Home About us Contact
|
Home About us Contact | ||
|
|
||
Related Peptides (relate + peptide)
Selected AbstractsReactions of Hydrogen Atoms with Met-Enkephalin and Related PeptidesCHEMISTRY - A EUROPEAN JOURNAL, Issue 7 2007Olivier Mozziconacci Abstract The reactions of hydrogen atoms with enkephalins and related peptides have been investigated by radiolytic methods in aqueous solutions and lipid vesicle suspensions. Pulse radiolysis experiments indicate that methionine residue (Met) is the main target. In Met-enkephalin (Tyr-Gly-Gly-Phe-Met) the attack of the hydrogen atom occurs to about 50,% on Met with formation of methanethiyl radical. The remaining percentage is divided roughly evenly between Tyr and Phe. With Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) the site of attack is limited to Tyr and Phe. Using a peptide,liposome (that is, 1-palmitoyl-2-oleoyl phosphatidylcholine vesicles) model, the cis,trans isomerization of phospholipids could be detected due to the catalytic action of thiyl radicals. The radiation chemical yields of the H. and, consequently of CH3S. radical, was modulated by the experimental conditions and the nature of peptide. Large amounts of trans lipids observed in phosphate buffer vesicle suspensions indicated the efficient role of double-bond isomerization as marker of Met-containing peptide damage. [source] The role of selected neuropeptides in pathogenesis of atopic dermatitisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2008J Salomon Abstract Background Atopic dermatitis (AD) is an inflammatory skin disease of a chronic course. The role of neuropeptides in pathogenesis of this disorder is probably not crucial; however, there is evidence that these substances influence the development and course of AD. Objective The aim of this study was to evaluate the plasma level of substance P, neuropeptide Y (NPY) and calcitonin gene related peptide (CGRP) in AD patients during exacerbation and remission of the disease. Material and methods Forty-nine patients with AD, aged 17 to 56 years, participated in the study. Among this group, there were 25 males (51%) and 24 females (49%). The disease lasted from 1 to 55 years. The severity of the disease was assessed with SCORAD index. The severity of pruritus was evaluated with Visual Analog Scale and a specially designed questionnaire. Neuropeptides plasma level was detected with radioimmunoassay. Results Substance P plasma level in AD patients during exacerbation and remission was significantly higher than in the control group. There was a negative correlation between substance P plasma level and total IgE level. CGRP plasma level during exacerbation of AD was significantly lower than in healthy controls and increased in the remission. Significantly higher CGRP concentration was observed in patients suffering from severe pruritus; however, both in patients with more and less severe pruritus, CGRP plasma level was lower than in controls. Higher CGRP plasma level was also observed in patients with more severe disease. NPY plasma level in patients with AD was significantly increased both during exacerbation and remission. During remission of AD, NPY concentration was higher than during exacerbation. [source] Nitric oxide specifically inhibits integrin-mediated platelet adhesion and spreading on collagenJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2008W. ROBERTS Summary.,Background:,Nitric oxide (NO) inhibits platelet adhesion to collagen, although the precise molecular mechanisms underlying this process are unclear. Objectives:,Collagen-mediated adhesion is a multifaceted event requiring multiple receptors and platelet-derived soluble agonists. We investigated the influence of NO on these processes. Results:,S-nitrosoglutathione (GSNO) induced a concentration-dependent inhibition of platelet adhesion to immobilized collagen. Maximal adhesion to collagen required platelet-derived ADP and TxA2. GSNO-mediated inhibition was lost in the presence of apyrase and indomethacin, suggesting that NO reduced the availability of, or signaling by, ADP and TxA2. Exogenous ADP, but not the TxA2 analogue U46619, reversed the inhibitory actions of GSNO on adhesion. Under adhesive conditions NO inhibited dense granule secretion but did not influence TxA2 generation. These data indicated that NO may block signaling by TxA2 required for dense granule secretion, thereby reducing the availability of ADP. Indeed, we found TxA2 -mediated activation of PKC was required to drive dense granule secretion, a pathway that was inhibited by NO. Because our data demonstrated that NO only inhibited the activation-dependent component of adhesion, we investigated the effects of NO on individual collagen receptors. GSNO inhibited platelet adhesion and spreading on ,2,1 specific peptide ligand GFOGER. In contrast, GSNO did not inhibit GPVI-mediated adhesion to collagen, or adhesion to the GPVI specific ligand, collagen related peptide (CRP). Conclusions:,NO targets activation-dependent adhesion mediated by ,2,1, possibly by reducing bioavailability of platelet-derived ADP, but has no effect on activation-independent adhesion mediated by GPVI. Thus, NO regulates platelet spreading and stable adhesion to collagen. [source] C-peptide prevents nociceptive sensory neuropathy in type 1 diabetesANNALS OF NEUROLOGY, Issue 6 2004Hideki Kamiya MD We examined the effects of C-peptide replacement on unmyelinated fiber function in the hind paw, sural nerve C-fiber morphometry, sciatic nerve neurotrophins, and the expression of neurotrophic receptors and content of neuropeptides in dorsal root ganglia in type 1 diabetic BB/Wor-rats. C-peptide replacement from onset of diabetes had no effect on hyperglycemia, but it significantly prevented progressive thermal hyperalgesia and prevented C-fiber atrophy, degeneration, and loss. These findings were associated with preventive effects on impaired availability of nerve growth factor and neurotrophin 3 in the sciatic nerve and significant prevention of perturbed expression of insulin, insulin growth factor,1, nerve growth factor, and neurotrophin 3 receptors in dorsal root ganglion cells. These beneficial effects translated into prevention of the decreased content of dorsal root ganglia nociceptive peptides such as substance P and calcitonin gene,related peptide. From these findings we conclude that replacement of insulinomimetic C-peptide prevents abnormalities of neurotrophins, their receptors, and nociceptive neuropeptides in type 1 BB/Wor-rats, resulting in the prevention of C-fiber pathology and nociceptive sensory nerve dysfunction. The data indicate that perturbed insulin/C-peptide action plays an important pathogenetic role in nociceptive sensory neuropathy and that C-peptide replacement may be of benefit in treating painful diabetic neuropathy in insulin-deficient diabetic conditions. Ann Neurol 2004 [source] Parathyroid hormone 1,34 inhibits terminal differentiation of human articular chondrocytes and osteoarthritis progression in ratsARTHRITIS & RHEUMATISM, Issue 10 2009Je-Ken Chang Objective Parathyroid hormone 1,34 (PTH[1,34]), a parathyroid hormone analog, shares the same receptor, PTH receptor 1, with parathyroid hormone,related peptide (PTHrP). This study was undertaken to address the hypothesis that PTH(1,34) inhibits terminal differentiation of articular chondrocytes and in turn suppresses the progression of osteoarthritis (OA). Methods We studied the effect of PTH(1,34) on human articular chondrocytes with azacytidine (azaC),induced terminal differentiation in vitro and on papain-induced OA in the knee joints of rats. In the in vitro study, we measured the levels of messenger RNA for SOX9, aggrecan, type II collagen, type X collagen, alkaline phosphatase (AP), Indian hedgehog (IHH), Bcl-2, and Bax by real-time polymerase chain reaction, levels of glycosaminoglycan (GAG) by dimethylmethylene blue assay, and rate of apoptosis by TUNEL staining. In the in vivo study, we evaluated the histologic changes in GAG, type II collagen, type X collagen, and chondrocyte apoptosis in the articular cartilage of rat knees. Results AzaC induced terminal differentiation of human chondrocytes, including down-regulation of aggrecan, type II collagen, and GAG and up-regulation of type X collagen, alkaline phosphatase, and IHH. Apoptosis was reversed by 3,10 days of treatment with 10 nM PTH(1,34). SOX9 expression was not changed by either azaC or PTH(1,34) treatment. Bcl-2 and Bax were up-regulated on day 10 and day 14, respectively, after azaC induction of terminal differentiation, but PTH(1,34) treatment did not reverse this effect. Furthermore, PTH(1,34) treatment reversed papain-induced OA changes (decreasing GAG and type II collagen, and increasing type X collagen and chondrocyte apoptosis) in the knee joints of rats. Conclusion Our findings indicate that PTH(1,34) inhibits the terminal differentiation of human articular chondrocytes in vitro and inhibits progression of OA in rats in vivo, and may be used to treat OA. [source] Topical PTH (1,34) is a novel, safe and effective treatment for psoriasis: a randomized self-controlled trial and an open trialBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2003M.F. Holick Summary Background There continues to be a need to develop new pharmacological approaches for treating the common skin disease psoriasis. Human skin produces parathyroid hormone related peptide. This peptide is a potent inhibitor of epidermal cell growth. Objectives A programme was initiated to determine whether an agonist of this peptide's receptor, PTH (1,34), could be developed as a drug to treat psoriasis. Methods PTH (1,34) was formulated in Novasome A® cream. Fifteen adult patients with chronic plaque psoriasis who had failed to respond to at least one standard treatment were enrolled in a randomized double-blinded placebo self-controlled trial. The patients topically applied to a 25-cm2 psoriatic lesion 0·1 g of either Novasome A® cream or Novasome A® cream that contained 20 ,g of PTH (1,34) twice a day for 2 months. At the end of the double-blind study, patients were enrolled in an open large area study. Ten patients applied PTH (1,34) (50 ,g per 0·1 g) once daily to their psoriatic lesions. The patients were evaluated for their global improvement and calcium metabolism. Results Novasome A® cream enhanced the percutaneous absorption of PTH (1,34) in human skin in comparison with formulations in propylene glycol or normal saline. Psoriatic lesions treated with PTH (1,34) showed marked improvement in scaling, erythema and induration. There was a 67·3% improvement in the global severity score for the lesion treated with PTH (1,34) compared with the placebo-treated lesion, which only showed a 17·8% improvement. Ten patients topically applied PTH (1,34) on all of their lesions in a stepwise manner. A Psoriasis Area and Severity Index score analysis of all the patients revealed improvement of 42·6% (P < 0·02). None of the patients experienced hypercalcaemia or hypercalciuria or developed any side-effect to the medication. Conclusions Patients who were resistant to at least one standard therapy for psoriasis had a remarkable improvement in their psoriasis when they applied PTH (1,34) to their lesion(s). No untoward toxicity was observed in any of the subjects. This pilot study suggests that topical PTH (1,34) is a safe and effective novel therapy for psoriasis. [source] Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin SBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2009JD Mitchell Neuromedin U (NMU) has been paired with the G-protein-coupled receptors (GPRs) NMU1 (formely designated as the orphan GPR66 or FM-3) and NMU2 (FM-4 or hTGR-1). Recently, a structurally related peptide, neuromedin S (NMS), which shares an amidated C-terminal heptapeptide motif, has been identified in both rat and human, and has been proposed as a second ligand for these receptors. Messenger RNA encoding NMU receptor subtypes shows differential expression: NMU1 is predominantly expressed in peripheral tissues, particularly the gastrointestinal tract, whereas NMU2 is abundant within the brain and spinal cord. NMU peptide parallels receptor distribution with highest expression in the gastrointestinal tract and specific structures within the brain, reflecting its major role in the regulation of energy balance. The NMU knockout mouse has an obese phenotype and, in agreement, the Arg165Trp amino acid variant of NMU-25 in humans, which is functionally inactive, co-segregated with childhood-onset obesity. Emerging physiological roles for NMU include vasoconstriction mediated predominantly via NMU1 with nociception and bone remodelling via NMU2. The NMU system has also been implicated in the pathogenesis of septic shock and cancers including bladder carcinoma and acute myeloid leukaemia. Intriguingly, NMS is more potent at NMU2 receptors in vivo where it has similar central actions in suppression of feeding and regulation of circadian rhythms to NMU. Taken together with its vascular actions, NMU may be a functional link between energy balance and the cardiovascular system and may provide a future target for therapies directed against the disorders that comprise metabolic syndrome. [source] Allergic airway inflammation induces tachykinin peptides expression in vagal sensory neurons innervating mouse airwaysCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2005Q. T. Dinh Summary Background Allergic airway inflammation has been shown to induce pro-inflammatory neuropeptides such as tachykinin peptides substance P (SP) and neurokinin A (NKA) together with related peptide like calcitonin gene-related peptide (CGRP) in nodose sensory neurons innervating guinea-pig airways. Objective The present study was designed to examine the effects of allergen sensitization and challenge on the SP/NKA expression in the jugular,nodose ganglion neurons innervating the murine airways. Methods Using retrograde neuronal tracing technique in combination with double-labelling immunohistochemistry, the expression of SP/NKA was investigated in a murine model of allergic airway inflammation. Results Allergic airway inflammation was found to induce the expression of SP/NKA (13.2±1.43% vs. 5.8±0.37%, P<0.01) in large-diameter (>20 ,m) vagal sensory neurons retrograde labelled with Fast blue dye from the main stem bronchi. Conclusion Based on the induction of tachykinins in airway-specific large-sized jugular,nodose ganglia neurons by allergic airway inflammation, the present study suggests that allergen sensitization and challenge may lead to de novo induction of tachykinins in neurons. This may partly contribute to the pathogenesis of airways diseases such as allergic airway inflammation. [source] FMRFamide gene and peptide expression during central nervous system development of the cephalopod mollusk, Idiosepius notoidesEVOLUTION AND DEVELOPMENT, Issue 2 2010Tim Wollesen SUMMARY Mollusks are a showcase of brain evolution represented by several classes with a varying degree of nervous system centralization. Cellular and molecular processes involved in the evolution of the highly complex cephalopod brain from a simple, monoplacophoran-like ancestor are still obscure and homologies on the cellular level are poorly established. FMRFamide (Phe-Ile-Arg-Phe-NH2)-related peptides (FaRPs) constitute an evolutionarily conserved and diverse group of neuropeptides in the central nervous system (CNS) of many metazoans. Herein, we provide a detailed description of the developing FMRFamide-like immunoreactive (Fa-lir) CNS of the pygmy squid Idiosepius notoides using gene expression analyses and immunocytochemistry. The open reading frame of the I. notoides FMRFamide gene InFMRF predicts one copy each of FIRFamide, FLRFamide (Phe-Leu-Arg-Phe-NH2), ALSGDAFLRFamide (Ala-Leu-Ser-Gly-Asp-Ala-Phe-Leu-Arg-Phe-NH2), and 11 copies of FMRFamide. Applying matrix-assisted laser desorption/ionization time-of-flight (ToF) mass spectrometry-based peptide profiling, we characterized all predicted FaRPs except ALSGDAFLRFamide. Two cell clusters express InFMRF and show FMRFamide-like-immunoreactivity within the palliovisceral ganglia, that is, the future posterior subesophageal mass, during the lobe differentiation phase. They project neurites via ventral axonal tracts, which form the scaffold of the future subesophageal mass. In the supraesophageal mass, InFMRF is first expressed during mid-embryogenesis in the superior and inferior buccal lobes. A neurite of the peduncle commissure represents the first Fa-lir element. Later, the sub- and supraesophageal mass interconnect via Fa-lir neurites and more brain lobes express InFMRF and FMRFamide-like peptides. InFMRF expression was observed in fewer brain lobes than Fa-lir elements. The early expression of InFMRF and FMRFamide-lir peptides in the visceral system and not the remaining CNS of the cephalopod I. notoides resembles the condition found in the majority of investigated gastropods. [source] Neuropeptide and neurohormone precursors in the pea aphid, Acyrthosiphon pisumINSECT MOLECULAR BIOLOGY, Issue 2010J. Huybrechts Abstract Aphids respond to environmental changes by developing alternative phenotypes with differing reproductive modes. Parthenogenetic reproduction occurs in spring and summer, whereas decreasing day lengths in autumn provoke the production of sexual forms. Changing environmental signals are relayed by brain neuroendocrine signals to the ovarioles. We combined bioinformatic analyses with brain peptidomics and cDNA analyses to establish a catalogue of pea aphid neuropeptides and neurohormones. 42 genes encoding neuropeptides and neurohormones were identified, of which several were supported by expressed sequence tags and/or peptide mass analyses. Interesting features of the pea aphid peptidome are the absence of genes coding for corazonin, vasopressin and sulfakinin and the presence of 10 different genes coding insulin related peptides, one of which appears to be very abundantly expressed. [source] Treatment of Skeletally Mature Ovariectomized Rhesus Monkeys With PTH(1-84) for 16 Months Increases Bone Formation and Density and Improves Trabecular Architecture and Biomechanical Properties at the Lumbar Spine,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2007John Fox PhD Abstract Histomorphometric studies of treatments for osteoporosis in humans are restricted to iliac crest biopsies. We studied the effects of PTH(1-84) treatment at the lumbar spine of skeletally mature ovariectomized rhesus monkeys. PTH increased bone turnover, rapidly normalized BMD, and increased vertebral compressive strength. PTH increased trabecular bone volume primarily by increasing trabecular number by markedly increasing intratrabecular tunneling. Introduction: Histomorphometric studies of the anabolic properties of PTH(1-84) (PTH) and related peptides in human bone are restricted to iliac crest biopsies. The ovariectomized (OVX) monkey is an accepted model of human postmenopausal bone loss and was used to study the effects of PTH treatment at clinically relevant skeletal sites. Materials and Methods: Skeletally mature rhesus monkeys were OVX or sham-operated and, after a bone depletion period of 9 months, treated daily for 16 months with PTH (5, 10, or 25 ,g/kg). Markers of bone formation (serum osteocalcin) and resorption (urine N-telopeptide [NTX]) and lumbar spine BMD were measured throughout the study. Trabecular architecture and vertebral biomechanical properties were quantified at 16 months. Results: PTH treatment induced dose-dependent increases in bone turnover but did not increase serum calcium. Osteocalcin was significantly increased above OVX controls by 1 month. NTX was significantly elevated at 1 month with the highest dose, but not until 12 months with the 5 and 10 ,g/kg doses. Lumbar spine BMD was 5% lower in OVX than in sham animals when treatment was started. All PTH doses increased BMD rapidly, with sham levels restored by 3,7 months with 10 and 25 ,g/kg and by 16 months with 5 ,g/kg. PTH treatment increased trabecular bone volume (BV/TV), primarily by increasing trabecular number, and dose-dependently increased bone formation rate (BFR) solely by increasing mineralizing surface. The largest effects on BV/TV and yield load occurred with the 10 ,g/kg dose. The highest dose reduced trabecular thickness by markedly increasing intratrabecular tunneling. Conclusions: PTH treatment of OVX rhesus monkeys increased bone turnover and increased BV/TV, BMD, and strength at the lumbar spine. All PTH doses were safe, but the 10 ,g/kg dose was generally optimal, possibly because the highest dose resulted in too marked a stimulation of bone remodeling. [source] Functional expression of corticotropin-releasing hormone (CRH) receptor 1 in cultured rat microgliaJOURNAL OF NEUROCHEMISTRY, Issue 2 2002Wei Wang Abstract Corticotropin-releasing hormone (CRH), known as a key regulator of the hypothalamic,pituitary,adrenal axis response to stress, elicits its biological effects by binding to two membrane receptors (CRH-R1 and CRH-R2). The present studies examined the presence of functional expression of CRH receptors in cultured microglia of rat. CRH-R1 mRNA and protein were detected by reverse transcriptase polymerase chain reaction (RT-PCR), western blotting and receptor chemical cross-linking assay in cultured microglia. CRH-R2 mRNA was undectable by RT-PCR. The radioligand binding analysis using [125I]Tyr-rat/human CRH revealed a high affinity binding site (Kd of 1.2 nm and Bmax of 84 fmol/mg of protein). Competition studies using CRH and related peptides indicated kinetic and pharmacological characteristics consistent with the CRH-R1 receptor subtype. Receptor chemical cross-linking assay demonstrated a single band of CRH receptor with a molecular weight of ,77 kDa, which was inhibited in the presence of excess unlabeled rat/human CRH in a dose-dependent manner and inhibited by a CRH receptor,antagonist astressin. Functional coupled cAMP production in cultured microglia was stimulated by exogenous addition of CRH and related peptides in a dose-dependent manner and blocked by astressin. Our findings suggest the functional expression of CRH-R1 receptor in rat microglia, indicating an important mechanism of interaction between immune and neuroendocrine systems in brain physiological and,pathological conditions. [source] Matrix formalism for site-specific binding of unstructured proteins to multicomponent lipid membranes,JOURNAL OF PEPTIDE SCIENCE, Issue 4 2008Vladimir B. Teif Abstract We describe a new approach to calculate the binding of flexible peptides and unfolded proteins to multicomponent lipid membranes. The method is based on the transfer matrix formalism of statistical mechanics recently described as a systematic tool to study DNA,protein,drug binding in gene regulation. Using the energies of interaction of the individual polymer segments with different membrane lipid species and the scaling corrections due to polymer looping, we calculate polymer adsorption characteristics and the degree of sequestration of specific membrane lipids. The method is applied to the effector domain of the MARCKS (myristoylated alanine rich C kinase substrate) protein known to be involved in signal transduction through membrane binding. The calculated binding constants of the MARCKS(151,175) peptide and a series of related peptides to mixed PC/PS/PIP2 membranes are in satisfactory agreement with in vitro experiments. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. [source] Interaction of S413 -PV cell penetrating peptide with model membranes: relevance to peptide translocation across biological membranesJOURNAL OF PEPTIDE SCIENCE, Issue 5 2007Miguel Mano Abstract Cell penetrating peptides (CPPs) have been successfully used to mediate the intracellular delivery of a wide variety of molecules of pharmacological interest both in vitro and in vivo, although the mechanisms by which the cellular uptake occurs remain unclear and controversial. Following our previous work demonstrating that the cellular uptake of the S413 -PV CPP occurs mainly through an endocytosis-independent mechanism, we performed a detailed biophysical characterization of the interaction of this peptide with model membranes. We demonstrate that the interactions of the S413 -PV peptide with membranes are essentially of electrostatic nature. As a consequence of its interaction with negatively charged model membranes, the S413 -PV peptide becomes buried into the lipid bilayer, which occurs concomitantly with significant peptide conformational changes that are consistent with the formation of a helical structure. Comparative studies using two related peptides demonstrate that the conformational changes and the extent of cell penetration are dependent on the peptide sequence, indicating that the helical structure acquired by the S413 -PV peptide is relevant for its nonendocytic uptake. Overall, our data suggest that the cellular uptake of the S413 -PV CPP is a consequence of its direct translocation through cell membranes, following conformational changes induced by peptide-membrane interactions. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source] Anatomy and functions of brain neurosecretory cells in dipteraMICROSCOPY RESEARCH AND TECHNIQUE, Issue 2 2003Sakiko Siga Abstract In the larval brain of dipteran insects, there are two medial and three lateral groups of neurons innervating the ring gland. One lateral group extends fibers to the corpus allatum. After metamorphosis, a large cluster of the medial group in the pars intercerebralis and two lateral groups in the pars lateralis innervate the retrocerebral complex and some neurons from the lateral group and a few from the medial group extend fibers to the corpus allatum in the adults. Neuropeptides such as insulin-like peptides, FMRFamide related peptides, Locusta -diuretic hormone, ,-pigment dispersing hormone, Manduca sexta -allatostatin, ovary ecdysteroidogenic hormone, and proctolin have been immunocytochemically revealed in medial groups in the pars intercerebralis, and FMRFamide related peptides, ,-pigment dispersing hormone, corazonin, and M. sexta -allatostatin in lateral groups in the pars lateralis of dipteran brains. In mosquitoes after the blood meal, ovary ecdysteroidogenic hormone from 2,3 pairs of medial neurosecretory cells is released at the corpus cardiacum to stimulate the ovaries to secrete ecdysteroid to cause ovarian development. In addition to ovarian development, removal and implantation experiments have shown that neurosecretory cells in the pars intercerebralis and pars lateralis are involved in control of reproductive diapause, cuticular tanning, sugar metabolism, and diures. Microsc. Res. Tech. 62:114,131, 2003. © 2003 Wiley-Liss, Inc. [source] Distribution and regulation of substance P-related peptide in the frog visual systemMICROSCOPY RESEARCH AND TECHNIQUE, Issue 4 2001Elizabeth A. DebskiArticle first published online: 10 AUG 200 Abstract Modulation of visual signal activity has consequences for both signal processing and for activity-dependent structuring mechanisms. Among the neuromodulatory agents found in visual areas are substance P (SP)-related peptides. This article reviews what is known about these substances in the amphibian retina and optic tectum with special emphasis on the leopard frog, Rana pipiens. It is found that the distribution of these SP-related peptides is remarkably similar to that seen in mammals. This suggests that study of model amphibian systems may significantly enhance our understanding of how neuropeptides contribute to visual system function and organization. Microsc. Res. Tech. 54:220,228, 2001. © 2001 Wiley-Liss, Inc. [source] Functions of corticotropin-releasing hormone in anthropoid primates: From brain to placentaAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 4 2006Michael L. Power Corticotropin-releasing hormone (CRH) is an ancient regulatory molecule. The CRH hormone family has at least four ligands, two receptors, and a binding protein. Its well-known role in the hypothalamic-pituitary-adrenal (HPA) axis is only one of many. The expression of CRH and its related peptides is widespread in peripheral tissue, with important functions in the immune system, energy metabolism, and female reproduction. For example, CRH is involved in the implantation of fertilized ova and in maternal tolerance to the fetus. An apparently unique adaptation has evolved in anthropoid primates: placental expression of CRH. Placental CRH stimulates the fetal adrenal zone, an adrenal structure unique to primates, to produce dehydroepiandrosterone sulfate (DHEAS), which is converted to estrogen by the placenta. Cortisol induced from the fetal and maternal adrenal glands by placental CRH induces further placental CRH expression, forming a positive feedback system that results in increasing placental production of estrogen. In humans, abnormally high placental expression of CRH is associated with pregnancy complications (e.g., preterm labor, intrauterine growth restriction (IUGR), and preeclampsia). Within anthropoid primates, there are at least two patterns of placental CRH expression over gestation: monkeys differ from great apes (and humans) by having a midgestational peak in CRH expression. The functional significance of these differences between monkeys and apes is not yet understood, but it supports the hypothesis that placental CRH performs multiple roles during gestation. A clearer understanding of the diversity of patterns of placental CRH expression among anthropoid primates would aid our understanding of its role in human pregnancy. Am. J. Hum. Biol. 18:431,447, 2006. © 2006 Wiley-Liss, Inc. [source] Enantiomer discrimination of peptides by tandem mass spectrometry: influence of the peptide sequence on chiral recognitionRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 22 2004Christoph Czerwenka The enantiomer discrimination of peptides by electrospray ionization tandem mass spectrometry is described. A cinchona alkaloid derivative, tert -butylcarbamoylquinine, is used as chiral selector. The chiral selector forms diastereomeric complexes with the peptide enantiomers in the liquid phase (methanolic solution), which are then transferred to the gas phase, where their dissociation behaviour is studied in an ion-trap mass spectrometer. Different degrees of dissociation of the diastereomeric complexes allow for the discrimination of the peptide enantiomers. The influence of the peptide sequence on enantiomer discrimination is discussed and molecular recognition information is derived by comparing the results obtained for related peptides. For dipeptides, small amino acid residues at the N-terminus and bulky side chains at the C-terminus were found to enhance chiral recognition, while for tripeptides the effects were rather irregular. Copyright © 2004 John Wiley & Sons, Ltd. [source] ,-melanocyte,stimulating hormone suppresses bleomycin-induced collagen synthesis and reduces tissue fibrosis in a mouse model of scleroderma: Melanocortin peptides as a novel treatment strategy for scleroderma?ARTHRITIS & RHEUMATISM, Issue 2 2009Agatha Kokot Objective Recently, we found that human dermal fibroblasts (HDFs) express melanocortin 1 receptors (MC-1R) that bind ,-melanocyte,stimulating hormone (,-MSH). In search of novel therapies for scleroderma (systemic sclerosis [SSc]), we used the bleomycin (BLM) model to investigate the effects of ,-MSH on collagen synthesis and fibrosis. Methods Collagen expression in HDFs was determined by real-time reverse transcription,polymerase chain reaction (RT-PCR) and Western blot analyses. Signal transduction studies included pharmacologic blockade, immunofluorescence analysis, Western blotting, and reporter,promoter assays. Oxidative stress was measured by fluorescence-activated cell sorter analysis, and anti,oxidative enzyme levels were determined by real-time RT-PCR and Western blot analyses. The effect of ,-MSH in the BLM mouse model of scleroderma was assessed by histologic, immunohistochemical, real-time RT-PCR, and protein analyses. Expression of MC-1R and pro-opiomelanocortin (POMC) in skin and HDF samples from patients with SSc was determined by RT-PCR and compared with that in samples from normal controls. Results Treatment with ,-MSH (and related peptides) suppressed BLM-induced expression of type I and type III collagen in HDFs, and this effect was cAMP-dependent. Neither BLM nor ,-MSH altered Smad signaling, but antioxidants inhibited BLM-induced collagen expression in vitro. In addition, ,-MSH suppressed BLM-induced oxidative stress and enhanced the expression of superoxide dismutase 2 (SOD2) and heme oxygenase 1 (HO-1). In the BLM mouse model, ,-MSH reduced skin fibrosis and collagen content and increased tissue levels of SOD2 and HO-1. In skin and HDFs from patients with SSc, both MC-1R and POMC messenger RNAs were detected, but there were no differences compared with healthy controls. Conclusion Alpha-melanocyte,stimulating hormone and related peptides that exert their effects via MC-1R may provide a novel antifibrogenic therapeutic tool for the treatment of fibrotic diseases such as scleroderma. [source] Prediction of Band Profiles of Mixtures of Bradykinin and Kallidin from Data Acquired by Competitive Frontal AnalysisBIOTECHNOLOGY PROGRESS, Issue 3 2003Dongmei Zhou The competitive adsorption isotherms of two closely related peptides, bradykinin and kallidin, were measured by frontal analysis on a Zorbax SB-C18 microbore column. An aqueous soluton at 20% acetonitrile (0.1% TFA) was used as the mobile phase. The competitive isotherm data were fitted to four different models: Langmuir, Bilangmuir, Langmuir-Freundlich, and Toth. These data fitted best to a Bilangmuir isotherm model. The influence of the pressure on the retention factors of the two peptides was found to be small and was not investigated in detail. The band profiles of large samples of the single components and of their mixtures were recorded. The overloaded profiles calculated using either the equilibrium-dispersive or POR model are in excellent agreement with the experimental profiles in all cases. Our results confirm that the competitive isotherm data derived from mixtures may suffice for a reasonably accurate prediction of the band profiles of all mixtures of the two components, provided their composition is close to 1/1. [source] Relevance of the C-terminal Arg-Phe sequence in ,2 -melanocyte-stimulating hormone (,2 -MSH) for inducing cardiovascular effects in conscious ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2000M J M A Nijsen The cardiovascular effects by ,2 -melanocyte-stimulating hormone (,2 -MSH) are probably not due to any of the well-known melanocortin subtype receptors. We hypothesize that the receptor for Phe-Met-Arg-Phe-amide (FMRFa) or Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-amide (neuropeptide FF; NPFFa), other Arg-Phe containing peptides, is the candidate receptor. Therefore, we studied various Arg-Phe containing peptides to compare their haemodynamic profile with that of ,2 -MSH(6,12), the most potent fragment of ,2 -MSH. Mean arterial pressure (MAP) and heart rate (HR) changes were measured in conscious rats after intravenous administration of ,2 -MSH related peptides. Phe-Arg-Trp-Asp-Arg-Phe-Gly (,2 -MSH(6,12)), FMRFa, NPFFa, Met-enkephalin-Arg-Phe-amide (MERFa), Arg-Phe-amide (RFa), acetyl-Phe-norLeu-Arg-Phe-amide (acFnLRFa) and desamino-Tyr-Phe-norLeu-Arg-Phe-amide (daYFnLRFa) caused a dose-dependent increase in MAP and HR. ,2 -MSH(6,12) showed the most potent cardiovascular effects (ED50=12 nmol kg,1 for ,MAP; 7 nmol kg,1 for ,HR), as compared to the other Arg-Phe containing peptides (ED50=177,292 nmol kg,1 for ,MAP; 130,260 nmol kg,1 for ,HR). Peptides, which lack the C-terminal Arg-Phe sequence (Lys-Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Pro-Gly (,2 -pro11 -MSH), desamino-Tyr-Phe-norLeu-Arg-[L-1,2,3,4 tetrahydroisoquinoline-3-carboxylic acid]-amide (daYFnLR[TIC]a) and Met-enkephalin (ME)), were devoid of cardiovascular actions. The results indicate that the baroreceptor reflex-mediated reduction of tonic sympathetic activity due to pressor effects is inhibited by ,2 -MSH(6,12) and that its cardiovascular effects are dependent on the presence of a C-terminal Arg-Phe sequence. It is suggested that the FMRFa/NPFFa receptor is the likely candidate receptor, involved in these cardiovascular effects. British Journal of Pharmacology (2000) 131, 1468,1474; doi:10.1038/sj.bjp.0703709 [source] Antimicrobial peptides from the skin of the Japanese mountain brown frog, Rana ornativentrisCHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2001J.B. Kim Abstract: Six peptides with antimicrobial activity were isolated from an extract of freeze-dried skin of the Japanese mountain brown frog Rana ornativentris. Two structurally related peptides (brevinin-20a GLFNVFKGALKTAGKHVAGSLLNQLKCKVSGGC, 11 nmol/g dried tissue, and brevinin-20b GIFNVFKGALKTAGKHVAGSLLNQLKCKVSGEC, 170 nmol/g) belong to the brevinin-2 family, previously identified in Asian and European, but not North American, Ranid frogs. Four peptides (temporin-1Oa FLPLLASLFSRLL.NH2, 13 nmol/g; temporin-1Ob FLPLIGKILGTI L.NH2, 350 nmol/g; temporin-1Oc FLPLLASLFSRLF.NH2, 14 nmol/g; and temporin-1Od FLPLLASLFSGLF.NH2, 8 nmol/g) are members of the temporin family first identified in the European common frog Rana temporaria but also found in the skins of North American Ranids. The brevinin-2 peptides showed broad-spectrum activity against the gram-positive bacterium, Staphylococcus aureus, the gram-negative bacterium, Escherichia coli and the yeast Candida albicans, whereas the temporins showed potent activity only against S. aureus. The brevinins and temporins belong to the class of cationic antimicrobial peptides that adopt an amphipathic ,-helical conformation but it is significant that temporin-1Od, which lacks a basic amino acid residue, is still active against S. aureus (minimum inhibitory concentration=13 µm compared with 2 µm for temporin-1Oa). This suggests that strong electrostatic interaction between the peptide and the negatively charged phospholipids of the cell membrane is not an absolute prerequisite for antimicrobial activity. [source] Reactions of Hydrogen Atoms with Met-Enkephalin and Related PeptidesCHEMISTRY - A EUROPEAN JOURNAL, Issue 7 2007Olivier Mozziconacci Abstract The reactions of hydrogen atoms with enkephalins and related peptides have been investigated by radiolytic methods in aqueous solutions and lipid vesicle suspensions. Pulse radiolysis experiments indicate that methionine residue (Met) is the main target. In Met-enkephalin (Tyr-Gly-Gly-Phe-Met) the attack of the hydrogen atom occurs to about 50,% on Met with formation of methanethiyl radical. The remaining percentage is divided roughly evenly between Tyr and Phe. With Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) the site of attack is limited to Tyr and Phe. Using a peptide,liposome (that is, 1-palmitoyl-2-oleoyl phosphatidylcholine vesicles) model, the cis,trans isomerization of phospholipids could be detected due to the catalytic action of thiyl radicals. The radiation chemical yields of the H. and, consequently of CH3S. radical, was modulated by the experimental conditions and the nature of peptide. Large amounts of trans lipids observed in phosphate buffer vesicle suspensions indicated the efficient role of double-bond isomerization as marker of Met-containing peptide damage. [source] WHAT MAKES A CGRP2 RECEPTOR?CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2007DL Hay SUMMARY 1Heterogeneity in the receptors for the neuropeptide calcitonin gene-related peptide (CGRP) has been apparent for nearly 20 years. This is most clearly manifested in the observation of CGRP8,37 -sensitive and -insensitive populations of CGRP-activated receptors. The pA2 values for CGRP8,37 in excess of 7 are widely considered to be the result of antagonism of CGRP1 receptors, whereas those below 7 are believed to be the consequence of antagonism of a second population of receptors, namely CGRP2 receptors. 2However, a multitude of pA2 values exist for CGRP8,37, spanning several log units, and as such no obvious clusters of values are apparent. Understanding the molecular nature of the receptors that underlie this phenomenon is likely to aid the development of selective pharmacological tools to progress our understanding of the physiology of CGRP and related peptides. Because there is active development of CGRP agonists and antagonists as therapeutics, such information would also further this pursuit. 3The CGRP1 receptor is pharmacologically and molecularly well defined as a heterodimer of the calcitonin receptor-like receptor (CL) and receptor activity modifying protein (RAMP) 1. The CL/RAMP1 complex is highly sensitive to CGRP8,37. Conversely, the constituents of the CGRP2 receptor have not been identified. In fact, there is little evidence for a distinct molecular entity that represents the CGRP2 receptor. 4Recent pharmacological characterization of receptors related to CGRP1 has revealed that some of these receptors may explain CGRP2 receptor pharmacology. Specifically, AMY1(a) (calcitonin receptor/RAMP1) and AM2 (CL/RAMP3) receptors can be activated by CGRP but are relatively insensitive to CGRP8,37. 5This, along with other supporting data, suggests that the ,CGRP2 receptor' that has been extensively reported in the literature may, in fact, be an amalgamation of contributions from a variety of CGRP-activated receptors. The use of appropriate combinations of agonists and antagonists, along with receptor expression studies, could allow such receptors to be separated. [source] | ||||||||||||||||||||||||||||