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Vasoactive Intestinal Peptide (vasoactive + intestinal_peptide)
Kinds of Vasoactive Intestinal Peptide Selected AbstractsGender Differences in the Expression of Galanin and Vasoactive Intestinal Peptide in Oestrogen-Induced Prolactinomas of Fischer 344 RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2004G. G. Piroli Abstract We have previously described a sexual dimorphism in oestrogen-induced anterior pituitary tumorigenesis in Fischer 344 rats, with female tumours averaging twice the size of those of males. Neonatal androgenization of female Fischer 344 rats with 100 µg of testosterone propionate reverted that effect, causing a ,male-like' phenotype. The peptides galanin and vasoactive intestinal peptide (VIP) are possible mediators of oestrogen effects on the anterior pituitary, including hyperprolactinemia and lactotroph proliferation. To further extend our previous findings, we investigated the expression of galanin and VIP in the anterior pituitary of control and oestrogenized male, female and neonatally androgenized female Fischer 344 rats. At 3 months of age, rats were deprived of their gonads and divided into control and diethylstilbestrol (DES)-treated groups. In the anterior pituitary of control rats, galanin and VIP immunoreactive cells were absent. However, in DES-treated rats, pituitaries from normal ovariectomized females showed higher number of galanin and VIP positive cells than pituitaries from neonatally androgenized ovariectomized females and gonadectomized males. This pattern correlated with changes in anterior pituitary weight and serum prolactin. Our study suggests that sexual differences in oestrogen-induced pituitary tumorigenesis could be due to the differential expression of galanin and VIP. Furthermore, our data support the fact that neonatal exposure to androgens, as in normal males and androgenized females, may condition the response of the pituitary gland to oestrogens in adult life. [source] Vasoactive intestinal peptide induces regulatory T cells during experimental autoimmune encephalomyelitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2006Amelia Fernandez-Martin Abstract CD4+CD25+ regulatory T cells (Treg) control the immune response to a variety of antigens, including self-antigens. Several models support the idea of the peripheral generation of CD4+CD25+ Treg from CD4+CD25, T cells. Little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4+CD25+ Treg. In this study we report on the capacity of the vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, to induce functional Treg in vivo during the development of experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. The administration of VIP to EAE mice results in the expansion of the CD4+CD25+, Foxp3-expressing T cells in the periphery and the nervous system, which inhibit encephalitogenic T cell activation. In addition to the increase in the number of CD4+CD25+ Treg, VIP induces more efficient suppressors on a per cell basis. The VIP-generated CD4+CD25+ Treg transfer suppression and significantly ameliorate the progression of the disease. [source] Vasoactive intestinal peptide acts via multiple signal pathways to regulate hippocampal NMDA receptors and synaptic transmissionHIPPOCAMPUS, Issue 9 2009Kai Yang Abstract Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide, which belongs to a superfamily of structurally related peptide hormones including pituitary adenylate cyclase-activating polypeptide (PACAP). Although several studies have identified the involvement of PACAP in learning and memory, little work has been done to investigate such a role for VIP. At least three receptors for VIP have been identified including the PACAP receptor (PAC1-R) and the two VIP receptors (VPAC receptors). VIP can activate the PAC1-R only if it is used at relatively high concentrations (e.g., 100 nM); however, at lower concentrations (e.g., 1 nM) it is selective for the VPAC receptors. Our lab has showed that PAC1-R activation signals through PKC/CAK,/Src pathway to regulate NMDA receptors; however, there is little known about the potential regulation of NMDA receptors by VPAC receptors. Our studies demonstrated that application of 1 nM VIP enhanced NMDA currents by stimulating the VPAC receptors as the effect was blocked by VPAC receptor antagonist [Ac-Tyr1, D-Phe2]GRF (1,29). This enhancement of NMDA currents was blocked by both Rp-cAMPS and PKI14,22 (they are highly specific PKA inhibitors), but not by the specific PKC inhibitor, bisindolylmaleimide I. In addition, the VIP-induced enhancement of NMDA currents was accentuated by inhibition of phosphodiesterase 4, which inhibits the degradation of cAMP. This regulation of NMDA receptors also required the scaffolding protein AKAP. In contrast, the potentiation induced by high concentration of VIP (e.g., 100 nM) was mediated by PAC1-R as well as by Src kinase. Overall, these results show that VIP can regulate NMDA receptors through different receptors and signaling pathways. © 2009 Wiley-Liss, Inc. [source] Analysis of innervation of human mesenteric vessels in non-inflamed and inflamed bowel , a confocal and functional studyNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2008D. Birch Abstract, We investigated the distribution and density of perivascular nerves in human mesenteric arteries and veins and their responses to noradrenaline (NA), ATP and neuropeptide Y (NPY) in control (non-inflamed) and inflamed bowel, using confocal microscopy and in vitro pharmacology. The density of innervation at the adventitial-medial border of arteries and within the medial muscle coat of veins was increased in inflammatory bowel disease (IBD). Expression of markers for both sympathetic nerves and sensory-motor nerves was significantly increased in IBD. Calcitonin gene-related peptide-containing sensory-motor nerves were present in control arteries and IBD, but not in control veins. The density of 5-hydroxytryptamine-containing nerves was variable in controls, but consistently increased (three to four times) in IBD. Vasoactive intestinal peptide (VIP) expression increased (doubled) in arteries and veins. Arteries and veins contracted to NA and ATP, but only veins constricted to NPY. ATP contractions were reduced in arteries and veins in IBD, while contractions to NA were only slightly reduced. Neuropeptide Y induced significantly greater (20%) contractions of IBD veins. In summary, the density of sympathetic and sensory-motor innervation of both mesenteric arteries and veins was increased in IBD. Both 5-hydroxytryptamine and VIP immunoreactivity were also increased. The responses of both arteries and veins to ATP, and to a lesser extent NA, were reduced in IBD while responses to NPY were greater in veins. Decreased responses to ATP indicate changes in purinergic-mediated transmission in the pathological state. [source] Genetic association of vasoactive intestinal peptide receptor with rheumatoid arthritis: Altered expression and signal in immune cellsARTHRITIS & RHEUMATISM, Issue 4 2008Mario Delgado Objective Vasoactive intestinal peptide (VIP) has been shown to be one of the endogenous factors involved in the maintenance of immune tolerance. Administration of VIP ameliorates clinical signs in various experimental autoimmune disorders. This study was undertaken to investigate whether the exacerbated inflammatory autoimmune response in rheumatoid arthritis (RA) might result directly from altered expression and/or signaling of VIP receptors in immune cells. Methods The effect of specific agonists of different VIP receptors on collagen-induced arthritis in mice was investigated by clinical and histologic assessment and measurement of cytokine and chemokine production. Expression of VIP receptor type 1 (VPAC1) in synovial cells and monocytes from RA patients was determined by flow cytometry. Potential associations of VPAC1 genetic polymorphisms with RA susceptibility were investigated. Results A VPAC1 agonist was very efficient in the treatment of experimental arthritis, and deficient expression of VPAC1 in immune cells of RA patients was associated with the predominant proinflammatory Th1 milieu found in this disease. Immune cells derived from RA patients were less responsive to VIP signaling than were cells from healthy individuals and showed reduced VIP-mediated immunosuppressive activity, rendering leukocytes and synovial cells more proinflammatory in RA. A significant association between multiple-marker haplotypes of VPAC1 and susceptibility to RA was found, suggesting that the reduced VPAC1 expression in RA-derived immune cells is associated with the described VPAC1 genetic polymorphism. Conclusion These findings are highly relevant to the understanding of RA pathogenesis. They suggest that VIP signaling through VPAC1 is critical to maintaining immune tolerance in RA. In addition, the results indicate that VPAC1 may be a novel therapeutic target in RA. [source] Motility-induced but not vasoactive intestinal peptide-induced increase in luminal alkalinization in rat duodenum is dependent on luminal Cl,ACTA PHYSIOLOGICA, Issue 2 2010L. Pihl Abstract Aim:, To investigate whether the motility- and the vasoactive intestinal peptide (VIP)-induced increase in luminal alkalinization in the duodenum is dependent on luminal Cl,. Methods:, Experiments were performed in anaesthetized rats in vivo. The proximal duodenum was perfused luminally with an isotonic solution, containing zero or low Cl, and the effects on luminal alkalinization, motility, fluid flux and epithelial permeability were determined. Parecoxib, a COX-2 inhibitor, was used to induce duodenal contractions. Results:, Control rats lacked duodenal wall contractions while parecoxib-treated ones exhibited contractions throughout the experiment. Most animals had a net fluid absorption during the perfusion with isotonic NaCl. Luminal alkalinization was about 100% higher in parecoxib-treated rats than in controls. Cl, -free solutions did not affect epithelial permeability or motility but decreased luminal alkalinization by ,50% and decreased net fluid absorption in both control and parecoxib-treated animals. Reduction in luminal Cl, decreased alkalinization in a concentration-dependent manner. The parecoxib-induced increase in alkalinization was markedly reduced in the absence of luminal Cl,. VIP increased luminal alkalinization and induced fluid secretion. The lack of luminal Cl, did not affect the VIP-induced increase in alkalinization but reduced fluid secretion. Conclusions:, The parecoxib-induced increase in luminal alkalinization is highly dependent on luminal Cl, and it is proposed that COX-2 inhibition, via induction of duodenal motility, enhances HCO3, efflux through stimulation of apical Cl,/HCO3, exchange in duodenal epithelial cells. Although the VIP-induced stimulation of fluid secretion is partly dependent on luminal Cl,, the VIP-induced increase in luminal alkalinization is not. [source] Different effects of electroacupuncture on esophageal motility and serum hormones in cats with esophagitisDISEASES OF THE ESOPHAGUS, Issue 2 2008X. Shuai SUMMARY., We aim to investigate the effects of different electroacupuncture (EA) frequencies at ST-36 on esophageal motility, and to compare the effect of EA on serum gastrin (GAS), motilin (MTL), and vasoactive intestinal peptide (VIP). Thirty-two cats were divided into four equal groups. All animals underwent a Heller myotomy. After esophagitis developed two frequencies (2/15 Hz or 2/100 Hz) of EA were delivered into ST-36 (LEA group [low EA], HEA group [high EA]). Animals submitted to EA on a non-point region (EANP) were used as controls (LEANP group, HEANP group), respectively. Esophageal motility was continuously monitored. The lower esophageal sphincter pressure (LESP) decreased significantly after myotomy. The LESP decreased in both LEA and LEANP cats, and in LEA cats the pressure decrease was greater. The LESP increased in the HEA group, which was higher than that in the HEANP group (P < 0.05). High-frequency EA significantly increased the peak amplitude in esophageal peristalsis. There was a decrease in serum GAS and MTL in LEA cats compared with LEANP cats (both P < 0.01). GAS and MTL were higher in the HEA group than in the HEANP group (both P < 0.01). Serum VIP decreased in the HEA group (P < 0.05), while it increased in the LEA group (P < 0.05), compared with EANP groups, respectively. EA with a high frequency at ST-36 enhances LESP as well as esophageal motility, while EA with a low frequency decreases LESP. The effect of EA is acupoint-specific, and this effect appears to be mediated through GAS, MTL and VIP. [source] Vasoactive intestinal peptide induces regulatory T cells during experimental autoimmune encephalomyelitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2006Amelia Fernandez-Martin Abstract CD4+CD25+ regulatory T cells (Treg) control the immune response to a variety of antigens, including self-antigens. Several models support the idea of the peripheral generation of CD4+CD25+ Treg from CD4+CD25, T cells. Little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4+CD25+ Treg. In this study we report on the capacity of the vasoactive intestinal peptide (VIP), an immunosuppressive neuropeptide, to induce functional Treg in vivo during the development of experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model. The administration of VIP to EAE mice results in the expansion of the CD4+CD25+, Foxp3-expressing T cells in the periphery and the nervous system, which inhibit encephalitogenic T cell activation. In addition to the increase in the number of CD4+CD25+ Treg, VIP induces more efficient suppressors on a per cell basis. The VIP-generated CD4+CD25+ Treg transfer suppression and significantly ameliorate the progression of the disease. [source] Pituitary adenylyl cyclase-activating polypeptide controls the proliferation of retinal progenitor cells through downregulation of cyclin D1EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2010Brian Njaine Abstract During retinal development, cell proliferation and exit from the cell cycle must be precisely regulated to ensure the generation of the appropriate numbers and proportions of the various retinal cell types. Previously, we showed that pituitary adenylyl cyclase-activating polypeptide (PACAP) exerts a neuroprotective effect in the developing retina of rats, through the cAMP,cAMP-dependent protein kinase (protein kinase A) (PKA) pathway. Here, we show that PACAP also regulates the proliferation of retinal progenitor cells. PACAP, PACAP-specific receptor (PAC1), and the receptors activated by both PACAP and vasoactive intestinal peptide (VIP), VPAC1 and VPAC2, are expressed during embryonic and postnatal development of the rat retina. Treatment of retinal explants with PACAP38 reduced the incorporation of [3H]thymidine as well as the number of 5-bromo-2,-deoxyuridine-positive and cyclin D1-positive cells. Pharmacological experiments indicated that PACAP triggers this antiproliferative effect through the activation of both PAC1 and VPACs, and the cAMP,PKA pathway. In addition, PACAP receptor activation decreased both cyclin D1 mRNA and protein content. Altogether, the data support the hypothesis that PACAP is a cell-extrinsic regulator with multiple roles during retinal development, including the regulation of proliferation in a subpopulation of retinal progenitor cells. [source] Mu opioid receptors are in discrete hippocampal interneuron subpopulationsHIPPOCAMPUS, Issue 2 2002Carrie T. Drake Abstract In the rat hippocampal formation, application of mu opioid receptor (MOR) agonists disinhibits principal cells, promoting excitation-dependent processes such as epileptogenesis and long-term potentiation. However, the precise location of MORs in particular inhibitory circuits, has not been determined, and the roles of MORs in endogenous functioning are unclear. To address these issues, the distribution of MOR-like immunoreactivity (-li) was examined in several populations of inhibitory hippocampal neurons in the CA1 region using light and electron microscopy. We found that MOR-li was present in many parvalbumin-containing basket cells, but absent from cholecystokinin-labeled basket cells. MOR-li was also commonly in interneurons containing somatostatin-li or neuropeptide Y-li that resembled the "oriens,lacunosum-moleculare" (O-LM) interneurons innervating pyramidal cell distal dendrites. Finally, MOR-li was in some vasoactive intestinal peptide- or calretinin-containing profiles resembling interneurons that primarily innervate other interneurons. These findings indicate that MOR-containing neurons form a neurochemically and functionally heterogeneous subset of hippocampal GABAergic neurons. MORs are most frequently on interneurons that are specialized to inhibit pyramidal cells, and are on a limited number of interneurons that target other interneurons. Moreover, the distribution of MORs to different neuronal types in several laminae, some relatively far from endogenous opioids, suggests normal functional roles that are different from the actions seen with exogenous agonists such as morphine. Hippocampus 2002;12:119,136. © 2002 Wiley-Liss, Inc. [source] Morphometric and immunohistochemical study of the abomasum of red deer during prenatal developmentJOURNAL OF ANATOMY, Issue 3 2007A. J. Masot Abstract The red deer is well suited to scientific study, given its economic importance as an animal to be hunted, and because it has a rich genetic heritage. However, there has been little research into the prenatal development of the stomach of ruminants in general, and none for the red deer. For this reason, we undertook histological evaluation of the ontogenesis of the abomasum in red deer. Histomorphometric and immunohistochemical analyses were carried out on 50 embryos and fetuses from the initial stages of prenatal life until birth. The animals were divided for test purposes into five experimental groups: group I [1.4,3.6 cm crown,rump length (CRL); 30,60 days, 1,25% of gestation]; group II (4.5,7.2 cm CRL; 67,90 days, 25,35% of gestation); group III (8,19 cm CRL; 97,135 days, 35,50% of gestation); group IV (21,33 cm CRL; 142,191 days, 50,70% of gestation) group V (36,40 cm CRL; 205,235 days, 75,100% of gestation). In the organogenesis of the primitive gastric tube of red deer, differentiation of the abomasum took place at 67 days, forming a three-layered structure: the epithelial layer (pseudostratified), pluripotential blastemic tissue and serosa. The abomasal wall displayed the primitive folds of the abomasum and by 97 days abomasal peak areas were observed on the fold surface. At 135 days the abomasal surface showed a single mucous cylindrical epithelium, and gastric pits were observed in the spaces between abomasal areas. At the bottom of these pits the first outlines of glands could be observed. The histodifferentiation of the lamina propria-submucosa, tunica muscularis and serosa showed patterns similar to those described for the forestomach of red deer. The abomasum of red deer during prenatal life, especially from 67 days of gestation, was shown to be an active structure with full secretory capacity. Its histological development, its secretory capacity (as revealed by the presence of neutral mucopolysaccharides) and its neuroendocrine nature (as revealed by the presence of positive non-neuronal enolase cells and the neuropeptides vasoactive intestinal peptide and neuropeptide Y) were in line with the development of the rumen, reticulum and omasum. Gastrin-immunoreactive cells first appeared in the abomasum at 142 days, and the number of positive cells increased during development. As for the number of gastrin cells, plasma gastrin concentrations increased throughout prenatal life. However, its prenatal development was later than that of the abomasum in sheep, goat and cow. [source] Age-associated plasticity in the intrinsic innervation of the ovine rumenJOURNAL OF ANATOMY, Issue 3 2003Helga Pfannkuche Abstract The rumen of adult sheep functions as a large fermentation chamber. In the newborn suckling ruminant, the rumen is bypassed and milk enters the abomasum directly. It was the aim of our study to investigate whether the transmitter content of intrinsic nerves changes with the developmental stage. The neurochemical code of myenteric neurons in the rumen from suckling lambs, fattened lambs and adult sheep was determined by using quadruple immunohistochemistry against choline-acetyltransferase (ChAT), nitric oxide synthase (NOS), substance P (SP) and vasoactive intestinal peptide (VIP). Three neurochemically distinct subpopulations were identified within the rumen. They expressed the code ChAT/,, ChAT/SP and NOS/VIP. The number of ChAT/SP neurons did not change during development. It was 62% in the newborn lamb and remained stable in fattened lambs (63%) and adult sheep (63%). By contrast, the number of ChAT/, neurons decreased significantly from 20% in suckling lambs to 11% and 7% in fattened lambs and adult sheep, respectively. Simultaneously, the proportion of NOS/VIP neurons increased from 16% in suckling lambs to 29% in adult sheep. The increase in the proportion of NOS/VIP immunoreactive neurons indicates an adaptation to large volumes of ingesta at the beginning of roughage intake and rumination. We conclude that the age-associated changes in neurochemical code of myenteric neurons in the forestomach are related to the adaption of the rumen to different functional properties during development. [source] Changes in vasoactive intestinal peptide in gingival crevicular fluid in response to periodontal treatmentJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2002Gerard J. Linden Abstract Aims: To evaluate the role of the anti-inflammatory neuropeptide vasoactive intestinal peptide (VIP) in periodontal health and disease and to determine the effects of periodontal treatment, resulting in a return to periodontal health, on the levels of VIP in gingival crevicular fluid (GCF). Methods: At baseline, 10 subjects with periodontitis (nine females, one male, mean age 43.0, SD 7.3) started a course of non-surgical periodontal treatment. Clinical indices were measured at one periodontitis and one clinically healthy site at an initial visit and at 8 weeks after the completion of treatment in each subject. A 30-s sample of GCF was collected from each test site using perio paper strips. The volume of GCF was measured and each sample subsequently analysed for VIP by radioimmunoassay. One healthy site was sampled from each member of a control group (10 females, mean age 29.9, SD 8.2 years) with clinically healthy gingiva and no periodontitis. Results: The clinical condition of all periodontitis sites improved as a result of periodontal treatment. The levels of VIP (pg/30 s sample) in periodontitis-affected sites fell significantly from 302.0 (SD 181.2) at the initial visit to 78.0 (54.4) after treatment, p = 0.007. The reduction in the concentration of VIP (pg/µL) in GCF from 524.3 (322.3) to 280.8 (280.2) was not statistically significant. The levels of VIP in clinically healthy sites fell from 115.5.5 (74.3) to 77.8 (32.3), n.s. and the concentration changed little from 883.8 (652.1) to 628.7 (323.3), n.s. There were substantially smaller amounts of VIP (25.8, SD 12.8) pg in healthy sites sampled from control subjects. Conclusions: VIP is present in GCF in greater quantities in periodontitis-affected than clinically healthy sites. In addition, the reduction in inflammation resulting from effective periodontal treatment is associated with a reduction in the levels of VIP in gingival crevicular fluid. [source] Selected pathological, immunohistochemical and ultrastructural changes associated with an infection by Diphyllobothrium dendriticum (Nitzsch, 1824) (Cestoda) plerocercoids in Coregonus lavaretus (L.) (Coregonidae)JOURNAL OF FISH DISEASES, Issue 8 2007B S Dezfuli Abstract The pathological changes induced by an infection of Diphyllobothrium dendriticum (Nitzsch, 1824) plerocercoids in powan, Coregonus lavaretus (L.), from Loch Lomond, Scotland, were assessed using immunohistochemical and ultrastructural techniques. In a sample of 26 powan, the occurrence of encysted plerocercoids of D. dendriticum on the outer surface of the stomach was 38.5% (n = 10) with the number of cysts ranging from 4 to 15 and measuring 4.2 ± 1.0 mm × 3.4 ± 0.9 mm (mean ± SD). Histological examination of intestinal samples also revealed plerocercoids (2,21) encapsulated within a proliferation of mesenteric fibrous tissues of the gastric wall and, occasionally, by the gut lamina propria-submucosa and lamina muscularis. In section, cysts were tri-layered and were formed from a series of concentric whorls of fibroblast and collagen fibre-based connective elements. The extent of necrosis within each muscle layer and the serosa of the stomach differed, notably within the latter that was marked by a chronic inflammatory reaction and fibrosis. Within the cyst and around it, a large number of degranulating mast cell/eosinophilic granule cells were seen, in addition to melano-macrophage centres. Immunohistochemical staining of sections of infected stomach revealed a high density of elements, in close proximity to plerocercoids, staining positive for serotonin, bombesin, substance P and galanin. Uninfected material did not present the same levels of activity. Sections through both infected and uninfected tissue were also tested for elements containing vasoactive intestinal peptide, met-enkephalin, calcitonin gene-related peptide, neuropeptide Y and nitric oxide synthase, but these were absent. [source] Broadly distributed nucleophilic reactivity of proteins coordinated with specific ligand binding activityJOURNAL OF MOLECULAR RECOGNITION, Issue 4 2005Yasuhiro Nishiyama Abstract Covalent nucleophile,electrophile interactions have been established to be important for recognition of substrates by several enzymes. Here, we employed an electrophilic amidino phosphonate ester (EP1) to study the nucleophilic reactivity of the following proteins: albumin, soluble epidermal growth factor receptor (sEGFR), soluble CD4 (sCD4), calmodulin, casein, ,-lactalbumin, ovalbumin, soybean trypsin inhibitor and HIV-1 gp120. Except for soybean trypsin inhibitor and ,-lactalbumin, these proteins formed adducts with EP1 that were not dissociated by denaturing treatments. Despite their negligible proteolytic activity, gp120, sEGFR and albumin reacted irreversibly with EP1 at rates comparable to the serine protease trypsin. The neutral counterpart of EP1 reacted marginally with the proteins, indicating the requirement for a positive charge close to the electrophilic group. Prior heating resulted in altered rates of formation of the EP1,protein adducts accompanied by discrete changes in the fluorescence emission spectra of the proteins, suggesting that the three-dimensional protein structure governs the nucleophilic reactivity. sCD4 and vasoactive intestinal peptide (VIP) containing phosphonate groups (EP3 and EP4, respectively) reacted with their cognate high-affinity binding proteins gp120 and calmodulin, respectively, at rates exceeding the corresponding reactions with EP1. Reduced formation of EP3,gp120 adducts and EP4,calmodulin adducts in the presence of sCD4 and VIP devoid of the phosphonate groups was evident, suggesting that the nucleophilic reactivity is expressed in coordination with non-covalent recognition of peptide determinants. These observations suggest the potential of EPs for specific and covalent targeting of proteins, and raise the possibility of nucleophile,electrophile pairing as a novel mechanism stabilizing protein,protein complexes. Copyright © 2005 John Wiley & Sons, Ltd. [source] Gender Differences in the Expression of Galanin and Vasoactive Intestinal Peptide in Oestrogen-Induced Prolactinomas of Fischer 344 RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2004G. G. Piroli Abstract We have previously described a sexual dimorphism in oestrogen-induced anterior pituitary tumorigenesis in Fischer 344 rats, with female tumours averaging twice the size of those of males. Neonatal androgenization of female Fischer 344 rats with 100 µg of testosterone propionate reverted that effect, causing a ,male-like' phenotype. The peptides galanin and vasoactive intestinal peptide (VIP) are possible mediators of oestrogen effects on the anterior pituitary, including hyperprolactinemia and lactotroph proliferation. To further extend our previous findings, we investigated the expression of galanin and VIP in the anterior pituitary of control and oestrogenized male, female and neonatally androgenized female Fischer 344 rats. At 3 months of age, rats were deprived of their gonads and divided into control and diethylstilbestrol (DES)-treated groups. In the anterior pituitary of control rats, galanin and VIP immunoreactive cells were absent. However, in DES-treated rats, pituitaries from normal ovariectomized females showed higher number of galanin and VIP positive cells than pituitaries from neonatally androgenized ovariectomized females and gonadectomized males. This pattern correlated with changes in anterior pituitary weight and serum prolactin. Our study suggests that sexual differences in oestrogen-induced pituitary tumorigenesis could be due to the differential expression of galanin and VIP. Furthermore, our data support the fact that neonatal exposure to androgens, as in normal males and androgenized females, may condition the response of the pituitary gland to oestrogens in adult life. [source] Innervation pattern and Ca2+ signalling in labial salivary glands of healthy individuals and patients with primary Sjögren's syndrome (pSS)JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 3 2000Anne Marie Pedersen Abstract: We have characterised the innervation pattern and intracellular Ca2+ -signalling in labial salivary glands (LSG) of 16 patients with primary Sjögren's syndrome (pSS) and 27 healthy controls. Numerous immunoreactive nerve fibers (IRF) containing vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) were found around acini, ducts and blood vessels. Substance P (SP)-, neuropeptide Y-, tyrosine hydroxylase- and nitric oxide synthase-IRF were mainly surrounding ducts and blood vessels. The majority of pSS patients had inflamed LSG and the presence of focal lymphocytic infiltrates (FI) were more frequent and pronounced as compared with healthy controls. In areas with normal or diffusely inflamed LSG tissue, pSS patients demonstrated the same distribution of IRF as healthy controls with similar histology. However, IRF were absent in central areas of FI both in pSS and age-matched healthy controls. Although all pSS patients had hyposalivation, stimulation with acetylcholine, norepinephrine, phenylephrine, isoproterenol, VIP, PACAP, SP, adenosine 5,-triphosphate and uridine 5,-triphosphate induced the same increase in the intracellular free Ca2+ concentration in LSG acini from both pSS patients and healthy controls, indicating the presence of functional receptor systems in vitro. [source] Human submucosal neurones regulate intestinal epithelial cell proliferation: evidence from a novel co-culture modelNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2003F. Toumi Abstract The role of the human enteric nervous system (ENS) in the control of the intestinal epithelium organization and proliferation is unknown. To address this issue, we developed a novel co-culture model, consisting of human submucosa containing the submucosal plexus and a human colonic epithelial monolayer. After 3 days in basal conditions (i.e. in absence of neuronal activation) epithelium disorganization and proliferation occurred. In contrast, electrical activation of submucosal neurones maintained monolayer organization and decreased cell proliferation. These effects were blocked by tetrodotoxin and a vasoactive intestinal peptide (VIP) receptor antagonist, and reproduced by VIP. In conclusion, our study suggests that the human ENS is involved in the control of epithelial cell proliferation. [source] Relation between stressful life events, neuropeptides and cytokines: results from the LISA birth cohort studyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 8 2008Gunda Herberth Stressful life events evidently have an impact on development of allergic diseases, but the mechanism linking stress to pathological changes of immune system function is still not fully understood. The aim of our study was to investigate the relationship between stressful life events, neuropeptide and cytokine concentrations in children. Within the LISAplus (Life style-Immune system-Allergy) study, blood samples from children of 6 yr of age were analysed for concentration of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM), substance P (SP) and the Th1/Th2 cytokines interferon-, (IFN-,) and interleukin (IL)-4. Life events such as severe disease or death of a family member, unemployment or divorce of the parents were assessed with a questionnaire filled in by the parents. For 234 children, blood analysis and questionnaire data regarding life events were available. Children with separated/divorced parents showed high VIP levels and high concentrations of the Th2 cytokine IL-4 in their blood. Severe diseases and death of a family member were neither associated with neuropeptide levels nor with cytokine concentrations. Unemployment of the parents was associated with decreased IFN-, concentrations in children's blood but not with neuropeptide levels, whereas children experiencing concomitant severe disease and death of a family member had reduced SP blood levels. The neuropeptide VIP might be a mediator between stressful life events and immune regulation contributing to the Th2 shifted immune response in children with separated/divorced parents. Unemployment of the parents was associated with immune regulation in children on the basis of a still unknown mechanism whereas reduced SP levels seem to have no effect on immune regulation. [source] Emerging treatments for pulmonary arterial hypertensionTHE CLINICAL RESPIRATORY JOURNAL, Issue 3 2008Dermot S. O'Callaghan Abstract Introduction:, Pulmonary arterial hypertension (PAH) is a rare, progressive disease for which no cure exists. However, improved understanding of underlying pathophysiological mechanisms has led to the development of several effective treatments that improve haemodynamics and functional status. Objective:, An overview of emerging pharmacological approaches to the management of PAH is presented. Materials and methods:, A Medline search was performed for studies describing novel treatments and potential therapeutic targets relevant to PAH. Results:, Several different treatments that modulate abnormalities in the prostacyclin, endothelin and nitric oxide pathways have shown efficacy in randomised, controlled studies and are now licensed for use for PAH patients with advanced disease. Furthermore, there is now encouraging long-term survival data associated with use of these agents. A number of other targets with therapeutic potential have also been identified, such as serotonin, platelet-derived growth factor and vasoactive intestinal peptide. Recently, strategies involving combinations of different PAH-specific agents have emerged as a promising approach for those failing monotherapy. Conclusion:, The therapeutic options available for PAH has improved considerably in recent years and is likely to expand in the future. Please cite this paper as: O'Callaghan DS. Emerging treatments for pulmonary arterial hypertension. The Clinical Respiratory Journal 2008; 2: 132,140. [source] The Cocaine- and Amphetamine-regulated Transcript (CART) Immunoreactivity in the Amygdala of the PigANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2010M. Równiak With 5 figures and 1 table Summary The distribution and morphology of neurons containing cocaine- and amphetamine-regulated transcript (CART) was investigated in the pig amygdala. CART- immunoreactive (CART-IR) cell bodies were rarely observed in the pig amygdala and most often they were present in the posterior (small-celled) parts of the basolateral and basomedial nuclei. In all other subdivisions only a small number of randomly scattered pericarya were present. In every region studied the CART-IR neurons formed a heterogeneous population consisting mostly of small, rounded or slightly elongated cell bodies, with a few poorly branched, smooth dendrites. In general, the morphological features of these cells clearly resembled non-pyramidal Golgi type II interneurons. Some randomly scattered CART-IR cell bodies were significantly larger and they demonstrated features of pyramidal-like Golgi type I projecting neurons. The highest densities of CART-IR fibres were evident within the central and medial nuclei. Moderate to high expression was found within the large-celled part of the basolateral nucleus and moderate to low levels in the lateral, basomedial and cortical nuclei. The routine double-labelling studies with antisera directed against CART and somatostatin (SOM), or neuropeptide Y (NPY), or cholecystokinin (CCK), or vasoactive intestinal peptide (VIP), or substance P (SP) demonstrated that, in general, these peptides do not co-exist in the CART-IR neurons. However, small subpopulations of the CART-IR fibres contained SOM, CCK, VIP or SP together. [source] A Quantitative Study of the Neural Changes Underlying Pyloric Stenosis in DogsANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2002R. M. Abel Summary This study aimed to quantify the neural changes in congenital pyloric stenosis in dogs and to study the comparative anatomy between this condition in dogs and that in infantile hypertrophic pyloric stenosis. Eight specimens from the pylorus of dogs with pyloric stenosis and six control specimens were examined using conventional histology and immunohistochemistry for a range of neural antigens. The changes in the proportion of nerves immunoreactive for each antigen were quantified and analysed statistically. The morphology of the nerves in the diseased dogs was similar to that in controls. Only vasoactive intestinal peptide was reduced in expression in dogs (median proportion in control dogs 0.57, in diseased dogs 0.17; P = 0.065). This study demonstrates both morphological similarities and significant differences between closely related conditions in dogs, humans and other species. [source] Behavioral regulators in the brain of neonatal chicksANIMAL SCIENCE JOURNAL, Issue 3 2007Mitsuhiro FURUSE ABSTRACT Domestic chickens are precocial and therefore have relatively well-developed processes at hatch. As a result, neonatal chicks grow well at hatch with no parental care. The regulation of food intake in animals, including domestic birds, is complicated. Just after hatching, neonatal chicks find their food by themselves and they can control their food intake. Recently, prolactin releasing peptide and gonadotropin-inhibitory hormone were confirmed as central orexigenic factors in the neonatal chick. Both peptides have a common structure as RFamide peptides. On the other hand, vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide, both belonging to the glucagon superfamily, were recognized as inhibitory. Broiler chicks have either a greater capability to acclimatize to novel environments, or a blunted hypothalamus-pituitary-adrenal axis compared with layer chicks. These differences are explained by higher melatonin concentrations in the pineal gland and other parts of the brain of broiler chicks since melatonin attenuates the stress response. Stressful behavior in chicks can be attenuated by neurotransmitters or by nutrients such as creatine, phosphatidylserine, L-serine and (-)-epigallocatechin gallate. It is suggested that the regulation of behavior is somewhat specific and can be attenuated by some manipulation in neonatal chicks. [source] Well-differentiated neuroendocrine carcinoma (malignant carcinoid) of the extrahepatic biliary tract: report of two cases and literature reviewAPMIS, Issue 8 2010SALVATORE SQUILLACI Squillaci S, Marchione R, Piccolomini M, Colombo F, Bucci F, Bruno M, Bisceglia M. Well-differentiated neuroendocrine carcinoma (malignant carcinoid) of the extrahepatic biliary tract: report of two cases and literature review. APMIS 2010; 118: 543,56. The objectives of this study were to evaluate the frequency of carcinoid tumors of the extrahepatic biliary ducts (EHBDs) and the pathologic progression and the role of surgery in the management of this disease. We describe two cases of malignant carcinoids of the EHBDs, which presented as common bile duct tumors in two adult male patients, aged 52 and 70 years, who were diagnosed histologically on surgical resection specimens. A comprehensive review of the literature has also been performed with a focus on survival data. Microscopically, the tumors presented herein were composed of relatively small rounded cells with a trabecular or nesting pattern. Both cases were diffusely immunopositive for chromogranin and synaptophysin, and one of them was also focally reactive with somatostatin and pancreatic polypeptide. There was no expression in any of these tumors of thyroid transcription factor-1 (TTF-1), gastrin, insulin, glucagon, vasoactive intestinal peptide (VIP) and prolactin. The tumor showed transmural invasion in both cases, with lymph node metastasis and subcapsular liver tissue infiltration in one. Both patients are alive with no evidence of disease 41 months and 59 months, respectively, after surgery. Despite being extremely uncommon, with only 70 cases reported to date, carcinoids should be included in the differential diagnosis of EHBD tumors. This study emphasizes the necessity of complete surgical resection as the gold standard treatment for these lesions, and the importance of a correct pathologic diagnosis for prognostic implications. [source] NO/cyclic GMP pathway mediates the relaxation of feline lower oesophageal sphincterAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2003C. H. Jun Summary 1 We examined the role of the NO/cyclic GMP (cyclic GMP) pathway in nitric oxide (NO)- and vasoactive intestinal peptide (VIP)-induced relaxation of feline lower oesophageal sphincter (LES). Furthermore, it was studied whether methylene blue, LY83583 and ODQ, which are soluble guanylate cyclase (sGC) inhibitors, could inhibit NO-induced relaxation. 2 The nitric oxide synthase (NOS) inhibitor, N -nitro- l -arginine (l -NNA) had no effect in sodium nitropruside (SNP)-induced relaxation, but 3-morpholinosydnonimine- N -ethylcarbamide (SIN-1)-induced relaxation was decreased by the pretreatment of l -NNA, which showed that SIN-1, not SNP, could activate NOS to cause relaxation. Methylene blue and LY83583 did not inhibit the relaxation by SNP and SIN-1. However, the more specific sGC inhibitor ODQ blocked the relaxation induced by NO donors. 3 To identify the relationship of NOS, sGC and adenylate cyclase in VIP-induced relaxation, tissue were pretreated with l -NNA and ODQ and SQ22536. These inhibitors produced significant inhibition of this response to VIP. The adenylyl cyclase inhibitor SQ 22536 also inhibited relaxation by VIP. 4 In conclusion, our data showed that SNP- and SIN-1-induced relaxation was mediated by sGC. Of sGC inhibitors, methylene blue and LY83583 were not adequate for the examination of NO donor-induced feline LES smooth muscle relaxation. VIP also caused relaxation by the pathway involving NO and cGMP and cAMP. [source] Effects of sepsis on mast cells in rat dura mater: influence of L -NAME and VIPBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2001F Tore The influence of lipopolysaccharide (LPS)-induced sepsis on the various mast cell phenotypes of rat dura mater were examined both by immunohistochemical and biochemical methods. Three different populations of mast cells were identified in control rats: connective tissue type mast cells (CTMC) which contain rat mast cell protease1 (RMCP1), histamine, serotonin and heparin, mucosal type mast cells (MMC) which contain RMCP2, histamine and serotonin, and intermediate type which contains both RMCP1 and RMCP2 and probably various proportions of amines and heparin. LPS (25 mg kg,1 i.p.) caused changes in the proportions of the various types of mast cells. The number of MMC and intermediate type mast cells significantly increased and the number of mast cells immunopositive for both heparin and serotonin significantly decreased. Biochemical analysis showed that the histamine concentration of dura increased while its serotonin concentration decreased. While vasoactive intestinal peptide (VIP) (25 ng kg,1 i.p.) appears to potentiate LPS effects on dura mater mast cells, non-selective inhibition of nitric oxide (NO) synthase by Ng -nitro- L -arginine methyl ester (L -NAME) (30 mg kg,1 i.p.) did not influence sepsis-induced mast cell changes. These findings suggest that mast cells of dura mater may play a role in brain protection during sepsis. British Journal of Pharmacology (2001) 134, 1367,1374; doi:10.1038/sj.bjp.0704412 [source] Effects of extracellular nucleotides and nucleosides on prostate carcinoma cellsBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2001Rodolphe Janssens The purpose of this work was to characterize the receptors involved in the action of nucleotides on the human prostate carcinoma cell lines LNCaP, PC-3 and DU145. Northern blotting revealed the presence of P2Y2, P2Y6 and P2Y11 messengers in the three cell lines. P2Y1 mRNA was only observed in the DU145 cells. In both PC-3 and DU145 cells, ATP and UTP stimulated inositol phosphate accumulation in an equipotent, equiactive and non-additive way, suggesting the involvement of P2Y2 receptors. ATP also increased cyclic AMP, but this effect is likely to result from degradation into adenosine and activation of A2 receptor. A2 receptor activation led to a synergistic enhancement of prostate-specific antigen secretion induced by vasoactive intestinal peptide. RT , PCR experiments detected the expression of the P2X4 and P2X5 receptors in the DU145 cells and the P2X4, P2X5 and P2X7 receptors in the PC-3 cells. The calcium influx induced by BzATP confirmed the functional expression of P2X receptors. ATP inhibited the growth of PC-3 and DU145 cells. This effect was mimicked neither by UTP nor by adenosine, indicating that it does not result from phospholipase C or adenylyl cyclase activation. On the contrary, in PC-3 cells, BzATP reproduced the effect of ATP, which was associated to a moderate decrease of proliferation and an increase of apoptosis. In DU145 cells, ATP was more potent than BzATP and growth inhibition was mainly associated with necrosis. We suggest that P2X receptors might be involved in the inhibition by nucleotides of prostate carcinoma cell growth. British Journal of Pharmacology (2001) 132, 536,546; doi:10.1038/sj.bjp.0703833 [source] Association of neuropeptides with Th1/Th2 balance and allergic sensitization in childrenCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2006G. Herberth Summary Background Among neurogenic factors, the neuropeptides have an important regulatory influence on immune system activity and may lead to allergic sensitization. Objective The aim of our study was to investigate the relationship of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM) and substance P (SP) on modulation of Th1/Th2 balance and allergic sensitization in children. Methods Within the LISAplus (Life style,Immune system,Allergy) study, blood samples of 321 six-year-old children were analysed for concentration of neuropeptides, Th1 and Th2 cytokines, transcription factors for T cell regulation and suppressors of cytokine signalling. In addition, samples were screened for specific IgE against inhalant and food allergens. Results Children with high SOM values showed a Th2 polarization and a reduced expression of FOXP3, the marker for regulatory T cells. High (VIP) levels correlated inversely with the expression of T cell transcription factors (Tbet and SOCS3). In contrast, elevated levels of SP were associated with reduced GATA3 and SOCS3 expression and with increased IFN-, concentrations. Allergic sensitization was more prevalent in children with higher SOM and VIP concentrations but not associated with SP levels. Conclusion Our data reveal an association between neuropeptides and modulatory effects on immune cells in vivo, especially on Th1/Th2 balance with a correlation to allergic sensitization in children. We suggest that elevated SOM and VIP concentrations and the inducing factors should be considered as allergy risk factors. [source] | ||||||||||||||||||||||||||||