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Receptor Types (receptor + type)
Terms modified by Receptor Types Selected AbstractsDifferential Role of Corticotrophin-Releasing Factor Receptor Types 1 and 2 in Stress-Induced Suppression of Pulsatile Luteinising Hormone Secretion in the Female RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2006X. F. Li Corticotrophin-releasing factor (CRF) plays a pivotal role in stress-induced suppression of the gonadotrophin-releasing hormone pulse generator. We have previously shown that type 2 CRF receptors (CRF2) mediate restraint stress-induced suppression of luteinising hormone (LH) pulses in the rat. The present study aimed: (i) to determine whether type 1 CRF receptors (CRF1) are also involved in this response to restraint and (ii) to investigate the differential involvement of CRF1 and CRF2 in the suppression of LH pulses in response to the metabolic perturbation of insulin-induced hypoglycemia and the innate immunological challenge of lipopolysaccharide (LPS). Ovariectomised rats with oestrogen replacement were implanted with intracerebroventricular (i.c.v.) and intravenous (i.v.) cannulae. Blood samples (25 µl) were collected every 5 min for 5 h for LH measurement. After 2 h of controlled blood sampling, rats were either exposed to restraint (1 h) or injected intravenously with insulin (0.25 IU/kg) or LPS (5 µg/kg). All three stressors suppressed LH pulses. The CRF1 antagonist SSR125543Q (11.5 µmol/rat i.v., 30 min before stressor) blocked the inhibitory response to restraint, but not hypoglycaemia or LPS stress. In addition to its effect on restraint, the CRF2 antagonist astressin2 -B (28 nmol/rat i.c.v., 10 min before insulin or LPS) blocked hypoglycaemia or LPS stress-induced suppression of LH pulses. These results suggest that hypoglycaemia and LPS stress-induced LH suppression involves activation of CRF2 while restraint stress-induced inhibition of LH pulses involves both CRF1 and CRF2. [source] A novel brain receptor is expressed in a distinct population of olfactory sensory neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2000Sidonie Conzelmann Abstract Three novel G-protein-coupled receptor genes related to the previously described RA1c gene have been isolated from the mouse genome. Expression of these genes has been detected in distinct areas of the brain and also in the olfactory epithelium of the nose. Developmental studies revealed a differential onset of expression: in the brain at embryonic stage 17, in the olfactory system at stage E12. In order to determine which cell type in the olfactory epithelium expresses this unique receptor type, a transgenic approach was employed which allowed a coexpression of histological markers together with the receptor and thus visualization of the appropriate cell population. It was found that the receptor-expressing cells were located very close to the basal membrane of the epithelium; however, the cells extended a dendritic process to the epithelial surface and their axons projected into the main olfactory bulb where they converged onto two or three glomeruli in the dorsal and posterior region of the bulb. Thus, these data provide evidence that this unique type of receptor is expressed in mature olfactory neurons and suggests that it may be involved in the detection of special odour molecules. [source] NMDA receptors influence the intracellular calcium concen-tration and the expression of differentiation markers in HaCaT cellsEXPERIMENTAL DERMATOLOGY, Issue 9 2004M. Fischer Ionotropic glutamate receptors (ligand-gated, ion-channel proteins) of the N -methyl- d -aspartate (NMDA) receptor type could enable a transmembranous calcium influx from the extracellular space. Though ionotropic glutamate receptors are predominantly neuronal receptors, they are also expressed in non-neuronal tissues like keratinocytes. Therefore, investigations were performed to study the function of NMDA receptors in HaCaT cells. The intracellular calcium concentration of HaCaT cells was studied under the influence of the selective receptor agonist NMDA and the selective NMDA antagonist MK-801. The proliferation of HaCaT cells was investigated using the crystal-violet method. Furthermore, the expression of Cytokeratin 10 and Filaggrin was examined in HaCaT cells after blocking NMDA receptors with MK-801. Using NMDA, there was a significant increase in the number of HaCaT cells showing elevated intracellular calcium concentration, at a dose between 25 µm and 1 mm (up to 84.6% of cells). The NMDA-associated calcium influx could be significantly suppressed by prior application of MK-801. There was no influence of NMDA on the proliferation of HaCaT cells. There was also no cytotoxic effect of NMDA (up to 1 mm). The expression of Cytokeratin 10 and Filaggrin could be suppressed by blocking NMDA receptors with MK-801. The investigations show that glutamate receptors of the NMDA-type play a role in the differentiation of HaCaT cells by regulating their intracellular calcium concentration. [source] Structure,function relationship of novel X4 HIV-1 entry inhibitors , L- and D-arginine peptide-aminoglycoside conjugatesFEBS JOURNAL, Issue 24 2007Ravi Hegde We present the design, synthesis, anti-HIV-1 and mode of action of neomycin and neamine conjugated at specific sites to arginine 6- and 9-mers d - and l -arginine peptides (APACs). The d -APACs inhibit the infectivity of X4 HIV-1 strains by one or two orders of magnitude more potently than their respective l -APACs. d -arginine conjugates exhibit significantly higher affinity towards CXC chemokine receptor type 4 (CXCR4) than their l -arginine analogs, as determined by their inhibition of monoclonal anti-CXCR4 mAb 12G5 binding to cells and of stromal cell-derived factor 1, (SDF-1,)/CXCL12 induced cell migration. These results indicate that APACs inhibit X4 HIV-1 cell entry by interacting with CXCR4 residues common to glycoprotein 120 and monoclonal anti-CXCR4 mAb 12G5 binding. d -APACs readily concentrate in the nucleus, whereas the l -APACs do not. 9-mer- d -arginine analogues are more efficient inhibitors than the 6-mer- d -arginine conjugates and the neomycin- d -polymers are better inhibitors than their respective neamine conjugates. This and further structure,function studies of APACs may provide new target(s) and lead compound(s) of more potent HIV-1 cell entry inhibitors. [source] Methylphenidate to adolescent rats drives enduring changes of accumbal Htr7 expression: implications for impulsive behavior and neuronal morphologyGENES, BRAIN AND BEHAVIOR, Issue 3 2009D. Leo Methylphenidate (MPH) administration to adolescent rodents produces persistent region-specific changes in brain reward circuits and alterations of reward-based behavior. We show that these modifications include a marked increment of serotonin (5-hydroxy-tryptamine) receptor type 7 (Htr7) expression and synaptic contacts, mainly in the nucleus accumbens, and a reduction of basal behavioral impulsivity. We show that neural and behavioral consequences are functionally related: administration of a selective Htr7 antagonist fully counteracts the MPH-reduced impulsive behavior and enhances impulsivity when administered alone in naive rats. Agonist-induced activation of endogenous Htr7 significantly increases neurite length in striatal neuron primary cultures, thus suggesting plastic remodeling of neuronal morphology. The mixed Htr (1a/7) agonist, 8-OH-DPAT, reduces impulsive behavior in adolescent rats and in naive adults, whose impulsivity is enhanced by the Htr7 antagonist. In summary, behavioral pharmacology experiments show that Htr7 mediates self-control behavior, and brain primary cultures experiments indicate that this receptor may be involved in the underlying neural plasticity, through changes in neuronal cytoarchitecture. [source] Phosphorylation and lipid raft association of fibroblast growth factor receptor-2 in oligodendrocytes,GLIA, Issue 9 2009M. R. Bryant Abstract Fibroblast growth factors (FGFs) and their receptors (FGFRs) initiate diverse cellular responses that contribute to the regulation of oligodendrocyte (OL) function. To understand the mechanisms by which FGFRs elicit these cellular responses, we investigated the phosphorylation of signal transduction proteins and the role of cholesterol-glycosphingolipid-enriched "lipid raft" microdomains in differentiated OLs. Surprisingly, we found that the most abundant tyrosine-phosphorylated protein in OLs was the 120-kd isoform of FGFR2 and that it was phosphorylated even in the absence of FGF2, suggesting a potential ligand-independent function for this receptor. Furthermore, FGFR2, but not FGFR1, was associated with lipid raft microdomains in OLs and myelin (but not in astrocytes). This provides the first evidence for the association of FGFR with TX-100-insoluble lipid raft fractions. FGFR2 phosphorylated the key downstream target, FRS2 in OLs. Raft disruption resulted in loss of phosphorylated FRS2 from lipid rafts, coupled with the loss of Akt but not of Mek or Erk phosphorylation. This suggests that FGFR2-FRS2 signaling in lipid rafts operates via the PI3-Kinase/Akt pathway rather than the Ras/Mek/Erk pathway, emphasizing the importance of microenvironments within the cell membrane. Also present in lipid rafts in OLs and myelin, but not in astrocytes, was a novel 52-kd isoform of FGFR2 that lacked the extracellular ligand-binding region. These results demonstrate that FGFR2 in OLs and myelin possess unique characteristics that are specific both to receptor type and to OLs and provide a novel mechanism to elicit distinct cellular responses that mediate both FGF-dependent and -independent functions. © 2008 Wiley-Liss, Inc. [source] Band 4.1 proteins are expressed in the retina and interact with both isoforms of the metabotropic glutamate receptor type 8JOURNAL OF NEUROCHEMISTRY, Issue 6 2008Melanie Rose Abstract The function of the CNS depends on the correct regulation of neurotransmitter receptors by interacting proteins. Here, we screened a retinal cDNA library for proteins interacting with the intracellular C-terminus of the metabotropic glutamate receptor isoform 8a (mGluR8a). The band 4.1B protein binds to the C-termini of mGluR8a and mGluR8b, co-localizes with these glutamate receptors in transfected mammalian cells, facilitates their cell surface expression and inhibits the mGluR8 mediated reduction of intracellular cAMP concentrations. In contrast, no interaction with 4.1B was observed for other mGluRs tested. Amino acids encoded by exons 19 and 20 of 4.1B and a stretch of four basic amino acids present in the mGluR8 C-termini mediate the protein interaction. Besides binding to 4.1B, mGluR8 isoforms interact with 4.1G, 4.1N, and 4.1R. Because band 4.1 transcripts undergo extensive alternative splicing, we analyzed the splicing pattern of interacting regions and detected a 4.1B isoform expressed specifically in the retina. Within this tissue, mGluR8 and 4.1B, 4.1G, 4.1N, and 4.1R show a comparable distribution, being expressed in both synaptic layers and in somata of the ganglion cell layer. In summary, our studies identified band 4.1 proteins as new players for the mGluR8 mediated signal transduction. [source] Expression and functional characterization of the mt1 melatonin receptor from rat brain in Xenopus oocytes: evidence for coupling to the phosphoinositol pathwayJOURNAL OF PINEAL RESEARCH, Issue 3 2001Cirstin Blumenau Melatonin-sensitive receptors were expressed in Xenopus laevis oocytes following an injection of mRNA from rat brain. The administration of 0.1,100 ,mol/L melatonin to voltage-clamped oocytes activates calcium-dependent chloride currents via a pertussis toxin-sensitive G protein and the phosphoinositol pathway. To determine which melatonin receptor type (mt1, MT2, MT3) is functionally expressed in the Xenopus oocytes, we used (i) agonists and antagonists of different receptor types to characterize the pharmacological profile of the expressed receptors and (ii) a strategy of inhibiting melatonin receptor function by antisense oligonucleotides. During pharmacological screening administration of the agonists 2-iodomelatonin and 2-iodo-N-butanoyl-5-methoxytryptamine (IbMT) to the oocytes resulted in oscillatory membrane currents, whereas the administration of the MT3 agonist 5-methoxycarbonylamino-N-acetyltryptamine (GR135,531) exerted no detectable membrane currents. The melatonin response was abolished by a preceding administration of the antagonists 2-phenylmelatonin and luzindole but was unaffected by the MT3 antagonist prazosin and the MT2 antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT). In the antisense experiments, in the control group the melatonin response occurred in 45 of 54 mRNA-injected oocytes (83%). Co-injection of the antisense oligonucleotide, corresponding to the mt1 receptor mRNA, caused a marked and significant reduction in the expression level (13%; P<0.001). In conclusion, the results demonstrate that injection of mRNA from rat brain in Xenopus oocytes induced the expression of the mt1 receptor which is coupled to the phosphoinositol pathway. [source] Subzonal organization of olfactory sensory neurons projecting to distinct glomeruli within the mouse olfactory bulbTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2003Olga Levai Abstract Olfactory sensory neurons located in the nasal neuroepithelium send their axons directly into the olfactory bulb, where they contact the dendrites of second-order neurons in specialized spherical structures called glomeruli; each sensory neuron projects to a single glomerulus. All neurons expressing the same odorant receptor gene are confined to distinct zones within the epithelium and converge their axons onto a small number of common glomeruli. In the present study, we analyzed transgenic mouse lines in which the projection of a neuron population expressing a particular receptor gene can be visualized as a result of axonal markers that are coexpressed. The target glomeruli could thus reproducibly be identified and allowed to deposit retrograde tracers precisely. After an appropriate incubation time, olfactory sensory neurons within distinct areas of the olfactory epithelium were labeled. The two subpopulations of neurons retrogradely stained by differently colored fluorescent dyes deposited at the dorsal and the dorsomedial glomerulus, respectively, were found to be segregated within distinct areas of the expression zone, where the cells expressing the same receptor type displayed a stochastic distribution. J. Comp. Neurol. 458:209,220, 2003. © 2003 Wiley-Liss, Inc. [source] The Enteric Nervous System II: Gastrointestinal FunctionsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2003Mark Berner Hansen This Minireview is part two of three and describes the role of the enteric nervous system in gastrointestinal functions (motility, exocrine and endocrine secretions, blood flow, and immune processes) in health and some disease states. In this context, the functional importance of the enteric nervous system for food intake, the gall bladder, and pancreas will be addressed. In specific, dysmotility, diarrhoea, constipation, non-occlusive intestinal ischaemia (intestinal angina), inflammation, cholelithiasis, cholecystitis, postcholecystectomy syndrome, and pancreatitis can be treated with neuroactive pharmacological agents. For example, serotonin receptor type four agonists can be used for the treatment of constipation, while nitric oxide synthesis inhibitors can be employed for the treatment of intestinal angina. [source] Mechanisms of adenosine-induced cytotoxicity and their clinical and physiological implicationsBIOFACTORS, Issue 1-4 2006Sharmila P. Seetulsingh-Goorah Abstract Extracellular ATP (ATPo) and adenosine are cytotoxic to several cancer cell lines, suggesting their potential use for anticancer therapy. Adenosine causes cytotoxicity, either when added exogenously or when generated from ATPo hydrolysis, via mechanisms which are not mutually exclusive and which involve, adenosine receptor activation, pyrimidine starvation and/or increases in intracellular S-adenosylhomocysteine: S-adenosylmethionine ratio. Given that adenosine also appears to protect against cytotoxicity via mechanisms including immunity against damage by oxygen free radicals, an understanding of the contribution of adenosine to ATPo-induced cytotoxicity is thus crucial, when considering any potential therapeutic use for these compounds. However, such an understanding has been largely hindered by the fact that many studies have not focused enough on the possibility that both ATPo and adenosine may mediate cytotoxicity in the same system. Such studies can benefit from use a range of ATPo concentrations when assessing the contribution of adenosine to ATPo-induced cytotoxicity. Whilst future molecular and pharmacological studies are needed to establish the nature of the cytotoxic adenosine receptor, it is possible that more than just one adenosine receptor type is involved and that the cytotoxic receptor(s) type is more likely to have a low affinity for adenosine. Activation of the adenosine receptor(s) would thus lead to cytotoxicity only at relatively high adenosine concentrations, while lower adenosine concentrations mediate non-cytotoxic physiological effects. [source] Regulatory mechanisms and functions of intermediate filaments: A study using site- and phosphorylation state-specific antibodiesCANCER SCIENCE, Issue 3 2006Ichiro Izawa Intermediate filaments (IF) form the structural framework of the cytoskeleton. Although histopathological detection of IF proteins is utilized for examining cancer specimens as reliable markers, the molecular mechanisms by which IF are involved in the biology of cancer cells are still unclear. We found that site-specific phosphorylation of IF proteins induces the disassembly of filament structures. To further dissect the in vivo spatiotemporal dynamics of IF phosphorylation, we developed site- and phosphorylation state-specific antibodies. Using these antibodies, we detected kinase activities that specifically phosphorylate type III IF, including vimentin, glial fibrillary acidic protein and desmin, during mitosis. Cdk1 phosphorylates vimentin-Ser55 from prometaphase to metaphase, leading to the recruitment of Polo-like kinase 1 (Plk1) to vimentin. Upon binding to Phospho-Ser55 of vimentin, Plk1 is activated, and then phosphorylates vimentin-Ser82. During cytokinesis, Rho-kinase and Aurora-B specifically phosphorylate IF at the cleavage furrow. IF phosphorylation by Cdk1, Plk1, Rho-kinase and Aurora-B plays an important role in the local IF breakdown, and is essential for the efficient segregation of IF networks into daughter cells. As another part of our research on IF, we have set out to find the binding partners with simple epithelial keratin 8/18. We identified tumor necrosis factor receptor type 1-associated death domain protein (TRADD) as a keratin 18-binding protein. Together with data from other laboratories, it is proposed that simple epithelial keratins may play a role in modulating the response to some apoptotic signals. Elucidation of the precise molecular functions of IF is expected to improve our understanding of tumor development, invasion and metastasis. (Cancer Sci 2006; 97: 167,174) [source] Ghrelin: more than a natural GH secretagogue and/or an orexigenic factorCLINICAL ENDOCRINOLOGY, Issue 1 2005E. Ghigo Summary Ghrelin, an acylated peptide produced predominantly by the stomach, has been discovered to be a natural ligand of the growth hormone secretagogue receptor type 1a (GHS-R1a). Ghrelin has recently attracted considerable interest as a new orexigenic factor. However, ghrelin exerts several other neuroendocrine, metabolic and also nonendocrine actions that are explained by the widespread distribution of ghrelin and GHS-R expression. The likely existence of GHS-R subtypes and evidence that the neuroendocrine actions, but not all the other actions, of ghrelin depend on its acylation in serine-3 revealed a system whose complexity had not been completely explored by studying synthetic GHS. Ghrelin secretion is mainly regulated by metabolic signals and, in turn, the modulatory action of ghrelin on the control of food intake and energy metabolism seems to be among its most important biological actions. However, according to a recent study, ghrelin-null mice are neither anorectics nor dwarfs and this evidence clearly depicts a remarkable difference from leptin null mice. Nevertheless, the original and fascinating story of ghrelin, as well as its potential pathophysiological implications in endocrinology and internal medicine, is not definitively cancelled by these data as GHS-R1a null aged mice show significant alterations in body composition and growth, in glucose metabolism, cardiac function and contextual memory. Besides potential clinical implications for natural or synthetic ghrelin analogues acting as agonists or antagonists, there are several open questions awaiting an answer. How many ghrelin receptor subtypes exist? Is ghrelin ,the' or just ,a' GHS-R ligand? That is, are there other natural GHS-R ligands? Is there a functional balance between acylated and unacylated ghrelin forms, potentially with different actions? Within the next few years suitable answers to these questions will probably be found, making it possible to gain a better knowledge of ghrelin's potential clinical perspectives. [source] A randomly assigned double-blind cross-over study examining the relative anti-parkinsonian tremor effects of pramipexole and pergolideEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2005P. Navan This study examined the relative anti-Parkinson's disease (PD) tremor potencies of pergolide and pramipexole in people with PD, using a 3-month double-blind cross-over design. Patients were randomly assigned to receive either pergolide and then pramipexole (n = 9) or vice versa (n = 8). The dose of the respective dopamine agonist was increased according to a titration schedule up to a maximum 1.5 mg t.d.s., with cross-over at 10 weeks. Assessments were performed at baseline, 4, 8 and 12 weeks. The primary outcome measures were the differences in the clinical (rest and postural) tremor scores on pergolide versus pramipexole. Seventeen PD patients (11 females and six males) with a mean age 68.4 years (range: 55,84 years) and a mean disease duration of 3.9 years (range: 2 months to 13 years) participated in the study. Twelve of the patients were taking other anti-parkinsonian medications. Two patients dropped out of the study whilst on pergolide. Fifteen of 16 patients were able to cross-over from one dopamine agonist to the other, without major retitration. There were no significant differences between the effects of the two drugs on the primary outcome measures, suggesting that the anti-PD tremor efficacies of dopaminergic medications are not dependent on differential affinities for dopamine receptor types. [source] A common gene exclusion mechanism used by two chemosensory systemsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2009Luca Capello Abstract Sensory coding strategies within vertebrates involve the expression of a limited number of receptor types per sensory cell. In mice, each vomeronasal sensory neuron transcribes monoallelically a single V1R pheromone receptor gene, chosen from a large V1R repertoire. The nature of the signals leading to this strict receptor expression is unknown, but is apparently based on a negative feedback mechanism initiated by the transcription of the first randomly chosen functional V1R gene. We show, in vivo, that the genetic replacement of the V1rb2 pheromone receptor coding sequence by an unrelated one from the odorant receptor gene M71 maintains gene exclusion. The expression of this exogenous odorant receptor in vomeronasal neurons does not trigger the transcription of odorant receptor-associated signalling molecules. These results strongly suggest that despite the different odorant and vomeronasal receptor expression sites, function and transduction cascades, a common mechanism is used by these chemoreceptors to regulate their transcription. [source] AMPA/kainate and NMDA-like glutamate receptors at the chromatophore neuromuscular junction of the squid: role in synaptic transmission and skin patterningEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Pedro A. Lima Abstract Glutamate receptor types were examined at the chromatophore synapses of the squids Alloteuthis subulata and Loligo vulgaris, where nerve-induced muscle contraction causes chromatophore expansion. Immunoblotting with antibody raised against a squid AMPA receptor (sGluR) demonstrated that AMPA/kainate receptors are present in squid skin. Application of l -glutamate evoked chromatophore muscle contractions in both ventral and dorsal skins, while NMDA was only active on a subpopulation of dorsal chromatophores. In dorsal skin, neurotransmission was partly blocked by either AMPA/kainate receptor antagonists (CNQX and DNQX) or NMDA receptor antagonists (AP-5 and MK-801) or completely blocked by simultaneous application of both classes of antagonists. In isolated muscle fibres, ionophoretic application of l -glutamate evoked fast inward CNQX- and DNQX-sensitive currents with reversal potentials around +14 mV and a high conductance to Na+. In fibres from dorsal skin only, a slower outward glutamate-sensitive current appeared at positive holding potentials. At negative potentials, currents were potentiated by glycine or by removing external Mg2+ and were blocked by AP-5 and MK-801. Glutamate caused a fast, followed by a slow, transient increase in cytoplasmic Ca2+. The slow component was increased in amplitude and duration by glycine or by lowering external Mg2+ and decreased by AP-5 and MK-801. In cells from ventral skin, no ,NMDA-like responses' were detected. Thus, while AMPA/kainate receptors mediated fast excitatory synaptic transmission and rapid colour change over the whole skin, activation of both AMPA/kainate and NMDA-like receptors in a subpopulation of dorsal chromatophores prolonged the postsynaptically evoked Ca2+ elevation causing temporally extended colour displays with behavioural significance. [source] Differential regulation of trkA and p75 in noradrenergic pelvic autonomic ganglion cells after deafferentation of their cholinergic neighboursEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2001Janet R. Keast Abstract In rats, following lesion of lumbar or sacral preganglionic axons, many pelvic ganglion cells undergo axogenesis to form baskets of terminals around select populations of nearby ganglion cells. The aim of the current study was to address mechanisms underlying initiation of this sprouting, focusing on a possible role for nerve growth factor (NGF). Immunohistochemical localization of NGF receptors (trkA and p75) showed that virtually all noradrenergic and a minority of cholinergic pelvic neurons expressed both receptors. Terminals immunoreactive for each substance were found in pelvic viscera. In pelvic ganglia, many glial cells expressed p75 but not trkA, and very few lumbar or sacral preganglionic neurons expressed either receptor. Lumbar and/or sacral preganglionic inputs were removed from ganglion cells by cutting the hypogastric, pelvic or both nerves, and tissues analysed 8 days later. Levels of receptor expression in noradrenergic pelvic ganglion cells were estimated by calculating the proportion that were receptor-immunopositive, and quantifying the intensity of trkA or p75 immunofluorescence. No lesion had a significant effect on trkA expression, however, a marked decrease in p75 occurred after cutting pelvic nerves, i.e. after deafferentation of neighbouring cholinergic neurons. These injuries appeared to cause little overall change in glial p75 expression. This study shows that manipulations that trigger sprouting from noradrenergic pelvic neurons cause downregulation of p75 but not trkA. Interestingly, this is occurring while some of their target organs are synthesizing high levels of NGF. This contrasts with other NGF-sensitive cells, in which one or both receptor types are upregulated by increased exposure to the ligand. The current study is also the first to show a change in p75 expression in neurons that are neither deafferented nor axotomized. [source] Opioids and opiates: analgesia with cardiovascular, haemodynamic and immune implications in critical illnessJOURNAL OF INTERNAL MEDICINE, Issue 2 2006P. E. MOLINA Abstract. Traumatic injury, surgical interventions and sepsis are amongst some of the clinical conditions that result in marked activation of neuroendocrine and opiate responses aimed at restoring haemodynamic and metabolic homeostasis. The central activation of the neuroendocrine and opiate systems, known collectively as the stress response, is elicited by diverse physical stressor conditions, including ischaemia, glucopenia and inflammation. The role of the hypothalamic,pituitary,adrenal axis and sympathetic nervous system in counterregulation of haemodynamic and metabolic alterations has been studied extensively. However, that of the endogenous opiates/opioid system is still unclear. In addition to activation of the opiate receptor through the endogenous release of opioids, pharmacotherapy with opiate receptor agonists is frequently used for sedation and analgesia of injured, septic and critically ill patients. How this affects the haemodynamic, cardiovascular, metabolic and immune responses is poorly understood. The variety of opiate receptor types, their specificity and ubiquitous location both in the central nervous system and in the periphery adds additional complicating factors to the clear understanding of their contribution to the stress response to the various physical perturbations. This review aims at discussing scientific evidence gathered from preclinical studies on the role of endogenous opioids as well as those administered as pharmacological agents on the host cardiovascular, neuroendocrine, metabolic and immune response mechanisms critical for survival from injury in perspective with clinical observations that provide parallel assessment of relevant outcome measures. When possible, the clinical relevance and corresponding scenarios where this evidence can be integrated into our understanding of the clinical implications of opiate effects will be examined. Overall, the scientific basis to enhance clinical judgment and expectations when using opioid sedation and analgesia in the management of the injured, septic or postsurgical patient will be discussed. [source] A family of octapamine receptors that specifically induce cyclic AMP production or Ca2+ release in Drosophila melanogasterJOURNAL OF NEUROCHEMISTRY, Issue 2 2005Sabine Balfanz Abstract In invertebrates, the biogenic-amine octopamine is an important physiological regulator. It controls and modulates neuronal development, circadian rhythm, locomotion, ,fight or flight' responses, as well as learning and memory. Octopamine mediates its effects by activation of different GTP-binding protein (G protein)-coupled receptor types, which induce either cAMP production or Ca2+ release. Here we describe the functional characterization of two genes from Drosophila melanogaster that encode three octopamine receptors. The first gene (Dmoa1) codes for two polypeptides that are generated by alternative splicing. When heterologously expressed, both receptors cause oscillatory increases of the intracellular Ca2+ concentration in response to applying nanomolar concentrations of octopamine. The second gene (Dmoa2) codes for a receptor that specifically activates adenylate cyclase and causes a rise of intracellular cAMP with an EC50 of ,3 × 10,8 m octopamine. Tyramine, the precursor of octopamine biosynthesis, activates all three receptors at ,,100-fold higher concentrations, whereas dopamine and serotonin are non-effective. Developmental expression of Dmoa genes was assessed by RT,PCR. Overlapping but not identical expression patterns were observed for the individual transcripts. The genes characterized in this report encode unique receptors that display signature properties of native octopamine receptors. [source] Glutamate Receptor Subunit ,2 Is Highly Expressed in a Novel Population of Glial-Like Cells in Rat Pineal Glands in CultureJOURNAL OF NEUROCHEMISTRY, Issue 3 2000Shouki Yatsushiro Abstract: The mammalian pineal gland uses L-glutamate as an intercellular chemical transmitter to regulate negatively melatonin synthesis. To receive glutamate signals, pinealocytes express at least three kinds of glutamate receptors: metabotropic receptor types 3 and 5 and an ionotropic receptor, GluR1. In this study, we examined whether or not the fourth class of ionotropic receptor, ,, which is known for its nondefinitive molecular function and its unique expression pattern in brain, is expressed in pineal gland. RT-PCR analyses with specific probes indicated the expression of mRNA of ,2 but not that of ,1 in pineal gland and cultured pineal cells. Western blotting analysis with polyclonal antibodies specific to the carboxyl-terminal region of the ,2 receptor recognized a single 110-kDa polypeptide of cerebellar membranes and specifically immunostained Purkinje cells. The ,2 antibodies recognized a 110-kDa polypeptide of pineal membranes and specifically immunostained huge glial-like cells with the occasional presence of several long, branching processes in a pineal cell culture. ,2 is not uniformly distributed throughout the cells and is relatively abundant at the periphery of the cell bodies and long processes, where the terminals of synaptophysin-positive processes of pinealocytes, a site for glutamate secretion, are frequently present. The ,2-positive cells constitute a very minor population among total pineal cells (,0.03%). Double immunolabeling with ,2 antibodies and antibodies against marker proteins for pineal interstitial cells clearly distinguishes ,2-positive pineal cells and other known interstitial cells, including glial fibrillary acidic protein- or vimentin-positive glial-like cells. These results indicated that the ,2 glutamate receptor is expressed in a novel subpopulation of pineal glial-like cells in culture and suggest the presence of a glutamate-mediated intercellular signal transduction mechanism between pinealocytes and ,2-expressing cells. The pineal cells may provide a good experimental system for studies on the function of glutamate receptor ,2. [source] Corticosteroid Effects on Serotonin Responses in Granule Cells of the Rat Dentate GyrusJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2001Y. J. G. Karten Abstract Granule cells in the rat dentate gyrus contain mineralocorticoid and glucocorticoid receptors to which the adrenal hormone corticosterone binds with differential affinity. These cells also express various receptor-subtypes for serotonin (5-HT), including the 5-HT1A receptor which mediates a membrane hyperpolarization accompanied by a decrease in membrane resistance. Earlier studies have shown that removal of corticosterone by adrenalectomy, particularly in the dentate gyrus, results in enhanced expression of the 5-HT1A receptor mRNA and increased 5-HT1A receptor binding capacity. This was normalized by activation of mineralocorticoid receptors or concurrent activation of both receptor types. In the present, intracellular recording study in vitro, we examined if the altered levels of 5-HT1A receptor mRNA and protein are associated with changes in the response to 5-HT. We found that the hyperpolarization and resistance decrease induced in granule cells by a submaximal (10 µM) dose of 5-HT were unaltered 2,4 days after adrenalectomy, indicating a dissociation between corticosteroid actions on 5-HT1A receptor mRNA/protein levels and functional responses to 5-HT. Subsequent occupation of mineralocorticoid receptors in vitro significantly suppressed the 5-HT induced change in resistance, 1,4 h after steroid application. Compared to this, concurrent activation of glucocorticoid receptors led to large responses to 5-HT. This modulation by steroids was not observed with a higher dose of 5-HT (30 µM). The data suggest that with moderate amounts of 5-HT, corticosteroids affect the information flow through the dentate gyrus such that excitatory transmission is promoted with predominant mineralocorticoid receptor activation and attenuated with additional glucocorticoid receptor occupation. [source] Expression and functional characterization of the mt1 melatonin receptor from rat brain in Xenopus oocytes: evidence for coupling to the phosphoinositol pathwayJOURNAL OF PINEAL RESEARCH, Issue 3 2001Cirstin Blumenau Melatonin-sensitive receptors were expressed in Xenopus laevis oocytes following an injection of mRNA from rat brain. The administration of 0.1,100 ,mol/L melatonin to voltage-clamped oocytes activates calcium-dependent chloride currents via a pertussis toxin-sensitive G protein and the phosphoinositol pathway. To determine which melatonin receptor type (mt1, MT2, MT3) is functionally expressed in the Xenopus oocytes, we used (i) agonists and antagonists of different receptor types to characterize the pharmacological profile of the expressed receptors and (ii) a strategy of inhibiting melatonin receptor function by antisense oligonucleotides. During pharmacological screening administration of the agonists 2-iodomelatonin and 2-iodo-N-butanoyl-5-methoxytryptamine (IbMT) to the oocytes resulted in oscillatory membrane currents, whereas the administration of the MT3 agonist 5-methoxycarbonylamino-N-acetyltryptamine (GR135,531) exerted no detectable membrane currents. The melatonin response was abolished by a preceding administration of the antagonists 2-phenylmelatonin and luzindole but was unaffected by the MT3 antagonist prazosin and the MT2 antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT). In the antisense experiments, in the control group the melatonin response occurred in 45 of 54 mRNA-injected oocytes (83%). Co-injection of the antisense oligonucleotide, corresponding to the mt1 receptor mRNA, caused a marked and significant reduction in the expression level (13%; P<0.001). In conclusion, the results demonstrate that injection of mRNA from rat brain in Xenopus oocytes induced the expression of the mt1 receptor which is coupled to the phosphoinositol pathway. [source] Immunohistochemical localization of angiotensin II receptor types 1 and 2 in the mesenteric artery from spontaneously hypertensive ratsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 8 2007Carmen Diniz Abstract Angiotensin II plays a crucial role in the control of blood pressure, acting at AT1 or AT2 receptors, and can act as a potent vasoconstrictor of the peripheral vasculature inducing hypertrophy, hyperplasia, or both, in resistance arteries. The aim of the present study was to investigate whether the pattern of distribution of angiotensin AT1 and AT2 receptors on mesenteric artery sections differs in spontaneously hypertensive rats (SHR) versus their respective controls (Wistar,Kyoto [WKY] rats). Immunohistochemistry using anti-AT1 or anti-AT2 antibodies was performed on perfused-fixed/paraffin-embedded mesenteric arteries from SHR and WKY rats. 3,3,-Diaminobenzidine tetrahydrochloride (DAB; activated by hydrogen peroxide) staining revealed distinct AT1 and AT2 labeling of all artery layers (adventitia, media and intima) from WKY rats, whereas in SHR an abundant AT1 labeling was found in both intima and adventitia and a sparser labeling in the media. There was a vast reduction of AT2 labeling throughout all layers. These results suggest a crucial role for AT2 receptors in the pathogenesis of hypertension. Microsc. Res. Tech., 2007. © 2007 Wiley-Liss, Inc. [source] The Renin-Angiotensin System in the Bovine Utero-Placental UnitREPRODUCTION IN DOMESTIC ANIMALS, Issue 3-4 2000AH Nielsen Contents Renin, angiotensin converting enzyme, and angiotensin II receptors are expressed in the bovine utero-placental unit, indicating the presence of a local renin-angiotensin system (RAS). Angiotensin II receptors of type AT1 and AT2 as well as non-AT1/non-AT2 binding sites were identified. The expression of both renin and the angiotensin II receptor types in the bovine utero-placental unit differs from that in humans. This fact is probably related to differences in placental architecture. The RAS in the bovine utero-placental unit might be important for growth processes in the endometrium and for placentation. It might also participate in the regulation of the utero-placental blood flow and secretion of hormones. Disturbances in the utero-placental RAS might cause a reduced utero-placental blood flow, intrauterine growth retarda_tion and intrauterine death. [source] The Effects of the ,2 -Adrenergic Receptor Agonists Clonidine and Rilmenidine, and Antagonists Yohimbine and Efaroxan, on the Spinal Cholinergic Receptor System in the RatBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2004Klas S. P. Abelson The cholinergic receptor system interacts with several other receptor types, such as ,2 -adrenergic receptors. To fully understand these interactions, the effects of various receptor ligands on the cholinergic system must be investigated in detail. This study was initiated to investigate the effects of the ,2 -adrenergic receptor agonists clonidine and rilmenidine and the ,2 -adrenergic receptor antagonists yohimbine and efaroxan on spinal cholinergic receptors in the rat. Spinal microdialysis was used to measure in vivo changes of acetylcholine after administration of the ligands, with or without nicotinic receptor blockade. In addition, in vitro binding properties of the ligands on muscarinic and nicotinic receptors were investigated. It was found that clonidine and rilmenidine increased, while yohimbine decreased spinal acetylcholine release. Efaroxan affected acetylcholine release differently depending on concentration. Nicotinic receptor blockade attenuated the effect of all ligands. All ligands showed poor binding affinity for muscarinic receptors. On the other hand, all ligands possessed affinity for nicotinic receptors. Clonidine and yohimbine binding was best fit to a one site binding curve and rilmenidine and efaroxan to a two site binding curve. The present study demonstrates that the tested ,2 -adrenergic receptor ligands affect intraspinal acetylcholine release in the rat evoked by nicotinic receptor mechanisms in vivo, and that they possess binding affinity to nicotinic receptors in vitro. The binding of ,2 -adrenergic receptor ligands to nicotinic receptors might affect the intraspinal release of acetylcholine. [source] Cell Signaling and Trafficking of Human Melanocortin Receptors in Real Time Using Two-photon Fluorescence and Confocal Laser Microscopy: Differentiation of Agonists and AntagonistsCHEMICAL BIOLOGY & DRUG DESIGN, Issue 4 2006Minying Cai Melanocortin hormones and neurotransmitters regulate a vast array of physiologic processes by interacting with five G-protein-coupled melanocortin receptor types. In the present study, we have systematically studied the regulation of individual human melanocortin receptor wild subtypes using a synthetic rhodamine-labeled human melanotropin agonist and antagonist, arrestins fused to green fluorescent protein in conjunction with two-photon fluorescence laser scanning microscopy and confocal microscopy. Stimulation of the melanocortin receptors by its cognate agonist triggered rapid arrestin recruitment and receptor internalization for all four human melanocortin receptors examined. Antagonists-bound melanocortin receptors, on the other hand, did not recruit , -arrestins, and remained in the cell membrane even after long-term (30 min) treatment. Agonist-mediated internalization of all melanocortin receptor subtypes was sensitive to inhibitors of clathrin-dependent endocytosis, but not to caveolae inhibitors. In summary, agonist-mediated internalization of all subtypes of melanocortin receptors are dependent upon ,-arrestin-mediated clathrin-coated pits, whereas, ,-arrestin-2 conjugated green fluorescence protein (,-arrestin-2-GFP) recruitment is not dependent on protein kinase A activation. Real time two-photon fluorescence laser scanning microscopy is a most powerful tool to study the dynamic processes in living cells and tissues, without inflicting significant and often lethal damage to the specimen. [source] | |||||||||||||||||||||||||