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David R. Thomas - One of the best experts on this subject based on the ideXlab platform.
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SB-699551-A (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4′-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), a novel 5-HT5A Receptor-selective antagonist, enhances 5-HT neuronal function: Evidence for an autoReceptor
Neuropharmacology, 2006Co-Authors: David R. Thomas, Sara A. Coggon, Ellen M. Soffin, Claire Roberts, James N.c. Kew, Raúl De La Flor, Lee A. Dawson, Victoria Anne Honey Fry, Stefania Faedo, Philip David HayesAbstract:Abstract This study utilised the selective 5-ht 5A Receptor antagonist, SB-699551-A (3-cyclopentyl- N -[2-(dimethylamino)ethyl]- N -[(4′-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), to investigate 5-ht 5A Receptor function in guinea pig brain. SB-699551-A competitively antagonised 5-HT-stimulated [ 35 S]GTPγS binding to membranes from human embryonic kidney (HEK293) cells transiently expressing the guinea pig 5-ht 5A Receptor (p A 2 8.1 ± 0.1) and displayed 100-fold selectivity versus the serotonin transporter and those 5-HT Receptor subtypes (5-HT 1A/B/D , 5-HT 2A/C and 5-HT 7 ) reported to modulate central 5-HT neurotransmission in the guinea pig. In guinea pig dorsal raphe slices, SB-699551-A (1 μM) did not alter neuronal firing per se but attenuated the 5-CT-induced depression in serotonergic neuronal firing in a subpopulation of cells insensitive to the 5-HT 1A Receptor-selective antagonist WAY-100635 (100 nM). In contrast, SB-699551-A (100 or 300 nM) failed to affect both electrically-evoked 5-HT release and 5-CT-induced inhibition of evoked release measured using fast cyclic voltammetry in vitro . SB-699551-A (0.3, 1 and 3 mg/kg s.c.) did not modulate extracellular levels of 5-HT in the guinea pig frontal cortex in vivo . However, when administered in combination with WAY-100635 (0.3 mg/kg s.c.), SB-699551-A (0.3, 1 or 3 mg/kg s.c.) produced a significant increase in extracellular 5-HT levels. These studies provide evidence for an autoReceptor role for the 5-ht 5A Receptor in guinea pig brain.
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5-HT5A Receptors as a therapeutic target.
Pharmacology & therapeutics, 2006Co-Authors: David R. ThomasAbstract:Abstract The 5-HT5A Receptor is enigmatic among 5-HT Receptors since, although the human Receptor was cloned in 1994, until recently, very little has been learnt about the function of the Receptor in native tissues. Findings from 5-HT5A Receptor mRNA localisation and immunolabelling studies have revealed widespread expression in the CNS, and have provided pointers to the potential functional role(s) of the Receptor. The expression of the 5-HT5A Receptor in raphe nuclei and in higher brain areas, such as the cerebral cortex and hippocampus, suggests a potential autoReceptor function whilst localisation in the suprachiasmatic nucleus (SCN) suggests a role in circadian rhythm control. Additionally, 5-HT5A Receptor knockout mouse phenotyping studies support a role in the control of exploratory behaviour. The lack of understanding of the role of the Receptor has been, in part, due to the lack of available selective 5-HT5A Receptor ligands. However, a selective 5-HT5A Receptor antagonist, 3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4′-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride (SB-699551-A), has recently been identified which appears to be a useful tool with which to elucidate the physiological function of the Receptor. Brain localisation and functional studies to date potentially implicate the Receptor in the control of circadian rhythms, mood and cognitive function, whilst gene association studies implicate the Receptor in the aetiology of schizophrenia. Although much is still to be learnt about the function of the 5-HT5A Receptor, on the basis of these findings, it can be speculated that 5-HT5A Receptor-selective ligands might show utility in psychiatric disorders such as schizophrenia and unipolar depression in which cognitive or mood disturbances are a feature.
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Discovery of a potent and selective 5-HT5A Receptor antagonist by high-throughput chemistry.
Bioorganic & medicinal chemistry letters, 2005Co-Authors: David F. Corbett, Tom D. Heightman, Stephen Moss, Steven Mark Bromidge, Sara A. Coggon, Mark J. Longley, Ana Maria Roa, Jennifer A. Williams, David R. ThomasAbstract:Abstract High-throughput screening of an array of biphenylmethylamines synthesised by high-throughput solid-phase chemistry resulted in the identification of compounds with high-affinity for the 5-HT5A Receptor. The structure–activity relationship within this series and further array synthesis led to the identification of the biphenylmethylamine derivative 11, a potent and selective 5-HT5A Receptor antagonist.
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Cloning and pharmacological characterisation of the guinea pig 5-HT5A Receptor.
European journal of pharmacology, 2004Co-Authors: David R. Thomas, Christopher G Larminie, Helen R Lyons, Andrew Fosberry, Matthew J Hill, Philip D HayesAbstract:The guinea pig 5-hydroxytryptamine(5A) (gp5-ht(5A)) Receptor was cloned from guinea pig brain using degenerate polymerase chain reaction (PCR) and shows 88%, 85% and 84% amino acid sequence identity versus the human, rat and mouse 5-ht(5A) Receptors, respectively. The Receptor was transiently expressed in human embryonic kidney (HEK) 293 cells. [(3)H]-Lysergic acid diethylamide (LSD) bound saturably to gp5-ht(5A)/HEK293 membranes with a K(d) of 2.3+/-0.1 nM and B(max) of 15.7+/-3.4 pmol/mg protein. The Receptor binding profile, determined by competition with [(3)H]LSD, correlated well with that for the human 5-ht(5A) Receptor. 5-HT stimulated [(35)S]GTPgammaS binding to gp5-ht(5A)/HEK293 membranes (pEC(50) 8.1+/-0.2), and the response was surmountably antagonised by methiothepin and ritanserin, giving apparent pK(B) values of 8.0 and 7.2, respectively. The 5-HT response was absent using membranes prepared from gp5-ht(5A)/HEK293 cells pretreated with pertussis toxin (PTX). These data suggest that the gp5-ht(5A) Receptor couples to G(i)-proteins in this expression system and shows a similar pharmacological profile to that for the human 5-ht(5A) Receptor.
Ricardo Miledi - One of the best experts on this subject based on the ideXlab platform.
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Expression of hippocampal serotonin Receptors 5-HT2C and 5-HT5A in a rat model of diet-induced obesity supplemented with tryptophan.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2015Co-Authors: Sarahi Lopez‐esparza, Laura C Berumen, Ricardo Miledi, Karla Padilla, Guadalupe García-alcocerAbstract:Food intake regulation is a complex mechanism that involves endogenous substances and central nervous system structures like hypothalamus or even hippocampus. The neurotransmitter serotonin is distinguished as food intake mediator; within its multiples Receptors, the 5-HT2C type is characterized by its inhibitory appetite action but there is no information about 5-HT5A Receptors involvement in obesity disease. It is also unknown if there are any changes in the Receptors expression in rats hippocampus with induced obesity during development through a high energy diet (HED) supplemented with tryptophan (W). To appreciate the Receptors expression pattern in the hippocampus, obesity was induced to young Sprague Dawley rats through a HED and supplemented with W. Immunocytochemical and western blot techniques were used to study the Receptor distribution and quantify the protein expression. The rats with HED diet developed obesity until week 13 of treatment. The 5-HT2C Receptor expression decreased in CA1, CA2, CA3 and DG of HED group; and also in CA2, CA3 and DG for HEDW group. The 5-HT5A Receptor expression only decreased in DG for HED group. Variations of the two serotonin Receptors subtypes support their potential role in obesity.
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Serotonin Receptor 5-HT5A in rat hippocampus decrease by leptin treatment.
Neuroscience letters, 2010Co-Authors: Guadalupe García-alcocer, Laura C Berumen, Angelina Rodríguez, Paulina Moreno-layseca, Jesica Escobar, Ricardo MilediAbstract:Hydroxytryptamine (5-HT) is involved in a variety of different physiological processes and behaviors through the activation of equally diverse Receptors subtypes. In this work we studied the changes on the expression of 5-HT5A Receptors in rat hippocampus induced by leptin, an adipocyte-derived hor- mone that has been reported to participate in the modulation of food intake and in adult hippocampal neurogenesis. To study the effect of leptin on the 5-HT5A Receptor gene expression a qRT-PCR was used and the distribution of those Receptors in the hippocampus was visualized by immunohistochemistry. Rats were separated in four groups: control (untreated rats), leptin-treated, serotonin-treated and lep- tin + serotonin treated. The results showed that even though the 5-HT5A gene expression did not change in the hippocampus of any of the treated groups, in the rats treated with leptin and serotonin, the specific immunostaining for the 5-HT5A serotonin Receptor decreased significantly in the dentate gyrus. © 2010 Elsevier Ireland Ltd. All rights reserved.
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Developmental expression of 5-HT5A Receptor mRNA in the rat brain
Neuroscience letters, 2005Co-Authors: Guadalupe García-alcocer, Gabriela Sarabia-altamirano, Ataúlfo Martínez-torres, Ricardo MilediAbstract:Abstract In the central nervous system, serotonin (5-HT) may function as a mitogen as well as a neurotransmitter; and its early appearance suggests a potential role in development. The present experiments were done to determine the localization of the mRNA coding for the 5-HT 5A Receptor during development of the rat brain. 5-HT 5A gene transcription was assessed by in situ hybridization, from E18 and during postnatal (PN) development. An intense signal of 5-HT 5A mRNA was found in the cerebral cortex and olfactory nucleus at E18, PN0 and PN5. A sharp decrease at PN11 was followed by an increase until reaching the adult level in the cerebral cortex; whereas in the olfactory nucleus, transcription remained weak. In contrast, in the hippocampal formation the signal was weak in the CA1, CA2 and CA3 regions at E18 and PO; increased at P5 and then decreased at P11 before attaining the adult level. We conclude that the gene coding for the 5-HT 5A Receptor is already active in the embryonic rat brain and is differentially expressed during development.
René Hen - One of the best experts on this subject based on the ideXlab platform.
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Human 5-HT5 Receptors: the 5-HT5A Receptor is functional but the 5-HT5B Receptor was lost during mammalian evolution
European journal of pharmacology, 2001Co-Authors: Régis Grailhe, Gregg W. Grabtree, René HenAbstract:Abstract We have isolated from a human genomic library the human 5-hydroxytryptamine 5-HT 5A and 5-HT 5B genes. The human 5-HT 5A gene encodes a protein with similar characteristics to its mouse homologue. When expressed in monkey COS-7 cells, the human 5-HT 5A Receptor displayed a high affinity for tritiated 5-carbamidotryptamine ([ 3 H]5-CT; K D =2.8 nM) and iodinated lysergic acid diethylamide ([ 125 I]LSD; K D =187 pM). These binding sites displayed the following displacement profile: Ergotamine>Methiothepin>5-CT, Ritanserin>5-HT. Reverse transcriptase polymerase chain reaction (RT-PCR) experiments revealed the presence of human 5-HT 5A mRNA in the central nervous system but not in peripheral organs. When expressed in Xenopus oocytes, the 5-HT 5A Receptor was able to couple to the inwardly rectifying K + channel, GIRK 1 . In contrast to the human 5-HT 5A gene and the mouse 5-HT 5B gene, the human 5-HT 5B gene does not encode a functional protein because its coding sequence is interrupted by stop codons. Our results suggest, therefore, that the 5-HT 5B Receptor has been lost during evolution after the divergence between rodents and primates. The 5-HT 5B Receptor is the first example of a brain-specific protein that is absent in human.
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Increased Exploratory Activity and Altered Response to LSD in Mice Lacking the 5-HT5A Receptor
Neuron, 1999Co-Authors: Régis Grailhe, Christian Waeber, Stephanie C. Dulawa, Jean P Hornung, Xiaoxi Zhuang, Dani Brunner, Mark A. Geyer, René HenAbstract:In order to determine the distribution and function of the 5-HT5A serotonin Receptor subtype, we generated knockout mice lacking the 5-HT5A gene. Comparative autoradiography studies of brains of wild-type (wt) and 5-HT5A knockout (5A-KO) mice revealed the existence of binding sites with high affinity for [125I]LSD that correspond to 5-HT5A Receptors and that are concentrated in the olfactory bulb, neocortex, and medial habenula. When exposed to novel environments, the 5A-KO mice displayed increased exploratory activity but no change in anxiety-related behaviors. In addition, the stimulatory effect of LSD on exploratory activity was attenuated in 5A-KO mice. These results suggest that 5-HT5A Receptors modulate the activity of neural circuits involved specifically in exploratory behavior and suggest that some of the psychotropic effects of LSD may be mediated by 5-HT5A Receptors.
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Putative 5-ht5 Receptors: localization in the mouse CNS and lack of effect in the inhibition of dural protein extravasation.
Annals of the New York Academy of Sciences, 1998Co-Authors: Christian Waeber, René Hen, Régis Grailhe, Michael A. MoskowitzAbstract:Putative 5-ht5 Receptor binding sites were visualized by in vitro autoradiography using [125I]LSD (in the presence of clozapine and spiperone) or [3H]5-carboxamidotryptamine (in the presence 8-OH-DPAT, GR127935 and spiperone). Under these conditions, no [3H]5-carboxamidotryptamine labeling was detected in the brain of mice lacking the gene encoding the putative 5-HT5A Receptor (knockout mice), whereas intermediate densities of binding sites were seen in the olfactory bulb and neocortex of wild-type mice. [125I]LSD labeled the same areas as [3H]5-carboxamidotryptamine in wild-type mice. High densities of [125I]LSD binding sites were observed in the medial habenula of wild type and knockout mice. 5-CT competed for [125I]LSD binding sites with an affinity of 2 nM in the olfactory bulb and neocortex of wild-type mice and an affinity of 30 nM in the habenula of knockout mice, suggesting that habenular labeling might be accounted for by putative 5-ht5b Receptors. In the presence of 5'-guanylylimidodiphosphate, 5-CT displaced [125I]LSD from putative 5-HT5A and 5-ht5b sites with a 6-times and 3-times lower affinity, respectively, suggesting that both Receptor subtypes are coupled to G proteins in brain. We also studied the inhibitory effect of 5-CT on dural neurogenic inflammation in knockout mice. In wild type mice, 3 ng/kg 5-CT inhibited dural protein extravasation by 60%. A similar effect was observed in knockout mice, even in the presence of the 5-HT1B Receptor antagonist GR127935. These results suggest that the inhibitory effects of 5-CT are not mediated by a site with the characteristics of the putative 5-ht5 Receptor.
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Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B Receptors define a new family of serotonin Receptors: cloning, functional expression, and chromosomal localization.
Molecular pharmacology, 1993Co-Authors: H Matthes, Ursula Boschert, Nourdine Amlaiky, R. Grailhe, Jean-luc Plassat, Françoise Muscatelli, Marie Geneviève Mattei, René HenAbstract:Serotonin [5-hydroxytryptamine (5-HT)] is a neuromodulator that mediates a wide range of physiological functions by activating multiple Receptors. Using a strategy based on amino acid sequence homology between 5-HT Receptors that interact with guanine nucleotide-binding proteins, we have isolated from a mouse brain library a cDNA encoding a new serotonin Receptor. Amino acid sequence comparisons revealed that this Receptor was a close relative of the previously identified 5-HT5 Receptor but was distant from all other 5-HT Receptor subtypes; we therefore named it 5-HT5B. When expressed in COS-7 cells, the 5-HT5B Receptor displayed a high affinity for the serotonergic radioligand 125I-lysergic acid diethylamide. Its pharmacological profile was distinct from that of all classic 5-HT Receptor subtypes. However, the high affinity of the 5-HT5B Receptor for 5-carboxamidotryptamine and its low affinity for sumatriptan indicated that it might correspond to recently described 5-HT1D-like binding sites that were labeled with [3H]5-carboxamidotryptamine and insensitive to sumatriptan. In situ hybridization experiments revealed that the 5-HT5B mRNA was expressed predominantly in the habenula and in the CA1 field of the hippocampus. We also determined the chromosomal localization of the 5-HT5A and 5-HT5B genes and of their human counterparts. The 5-HT5A gene colocalized with the mouse mutation reeler and the human mutation holoprosencephaly type 3, which both result in abnormal brain development, raising the possibility that the 5-HT5A Receptor plays a role in brain development.
Beatriz Godínez-chaparro - One of the best experts on this subject based on the ideXlab platform.
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Antiallodynic effect induced by [6]-gingerol in neuropathic rats is mediated by activation of the serotoninergic system and the nitric oxide-cyclic guanosine monophosphate-adenosine triphosphate-sensitive K+ channel pathway.
Phytotherapy Research, 2018Co-Authors: Alfonso Mata-bermudez, Teresa Izquierdo, Espinosa De Los Monteros-zuñiga, Arrigo Coen, Beatriz Godínez-chaparroAbstract:The present study evaluated the possible antiallodynic effect induced by [6]-gingerol in rats with L5-L6 spinal nerve ligation (SNL). Moreover, we determined the possible mechanism underlying the antiallodynic effect induced by [6]-gingerol in neuropathic rats. The animals underwent L5-L6 SNL for the purpose of developing tactile allodynia. Tactile allodynia was measured with von Frey filaments. Intrathecal administration of [6]-gingerol reversed SNL-induced tactile allodynia. The [6]-gingerol-induced antiallodynic effect was prevented by the intrathecal administration of methiothepin (30 μg per rat; nonselective 5-hydroxytryptamine [5-HT] antagonist), WAY-100635 (6 μg per rat; selective 5-HT1A Receptor antagonist), SB-224289 (5 μg per rat; selective 5-HT1B Receptor antagonist), BRL-15572 (4 μg per rat; selective 5-HT1D Receptor antagonist), and SB-659551 (6 μg per rat; selective 5-HT5A Receptor antagonist), but naloxone (50 μg per rat; nonselective opioid Receptor antagonist) did not prevent the [6]-gingerol-induced antiallodynic effect. Moreover, intrathecal administration of Nω-nitro-l-arginine methyl ester (100 μg per rat; nonselective nitric oxide [NO] synthase inhibitor), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 μg per rat; inhibitor of guanylate cyclase), and glibenclamide (50 μg per rat; channel blocker of adenosine triphosphate [ATP]-sensitive K+ channels) prevented the [6]-gingerol-induced antiallodynic effect. These data suggest that the antiallodynic effect induced by [6]-gingerol is mediated by the serotoninergic system involving the activation of 5-HT1A/1B/1D/5A Receptors, as well as the NO-cyclic guanosine monophosphate-ATP-sensitive K+ channel pathway but not by the opioidergic system.
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Antinociceptive effect of (-)-epicatechin in inflammatory and neuropathic pain in rats.
Behavioural pharmacology, 2018Co-Authors: Geovanna Nallely Quiñonez-bastidas, Beatriz Godínez-chaparro, Jorge Baruch Pineda-farias, Vinicio Granados-soto, Francisco J. Flores-murrieta, Juan Rodríguez-silverio, Juan Gerardo Reyes-garcía, Héctor Isaac Rocha-gonzálezAbstract:The aim of this study was to investigate the antinociceptive potential of (-)-epicatechin and the possible mechanisms of action involved in its antinociceptive effect. The carrageenan and formalin tests were used as inflammatory pain models. A plethysmometer was used to measure inflammation and L5/L6 spinal nerve ligation as a neuropathic pain model. Oral (-)-epicatechin reduced carrageenan-induced inflammation and nociception by about 59 and 73%, respectively, and reduced formalin- induced and nerve injury-induced nociception by about 86 and 43%, respectively. (-)-Epicatechin-induced antinociception in the formalin test was prevented by the intraperitoneal administration of antagonists: methiothepin (5-HT1/5 Receptor), WAY-100635 (5-HT1A Receptor), SB-224289 (5-HT1B Receptor), BRL-15572 (5-HT1D Receptor), SB-699551 (5-HT5A Receptor), naloxone (opioid Receptor), CTAP (μ opioid Receptor), nor-binaltorphimine (κ opioid Receptor), and 7-benzylidenenaltrexone (δ1 opioid Receptor). The effect of (-)-epicatechin was also prevented by the intraperitoneal administration of L-NAME [nitric oxide (NO) synthase inhibitor], 7-nitroindazole (neuronal NO synthase inhibitor), ODQ (guanylyl cyclase inhibitor), glibenclamide (ATP-sensitive K channel blocker), 4-aminopyridine (voltage-dependent K channel blocker), and iberiotoxin (large-conductance Ca-activated K channel blocker), but not by amiloride (acid sensing ion channel blocker). The data suggest that (-)-epicatechin exerts its antinociceptive effects by activation of the NO-cyclic GMP-K channels pathway, 5-HT1A/1B/1D/5A serotonergic Receptors, and μ/κ/δ opioid Receptors.
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Anti-allodynic effect of mangiferin in neuropathic rats: Involvement of nitric oxide-cyclic GMP-ATP sensitive K+ channels pathway and serotoninergic system.
Pharmacology Biochemistry and Behavior, 2016Co-Authors: Antonio Espinosa De Los Monteros-zuñiga, Teresa Izquierdo, Geovanna Nallely Quiñonez-bastidas, Héctor Isaac Rocha-gonzález, Beatriz Godínez-chaparroAbstract:The neurobiology of neuropathic pain is caused by injury in the central or peripheral nervous system. Recent evidence points out that mangiferin shows anti-nociceptive effect in inflammatory pain. However, its role in inflammatory and neuropathic pain and the possible mechanisms of action are not yet established. The purpose of this study was to determine the possible anti-allodynic effect of mangiferin in rats with spinal nerve ligation (SNL). Furthermore, we sought to investigate the possible mechanisms of action that contribute to these effects. Mechanical allodynia to stimulation with the von Frey filaments was measured by the up and down method. Intrathecal administration of mangiferin prevented, in a dose-dependent fashion, SNL-induced mechanical allodynia. Mangiferin-induced anti-allodynia was prevented by the intrathecal administration of L-NAME (100μg/rat, non-selective nitric oxide synthase inhibitor), ODQ (10μg/rat, inhibitor of guanylate-cyclase) and glibenclamide (50μg/rat, channel blocker of ATP-sensitive K+ channels). Moreover, methiothepin (30μg/rat, non-selective 5-HT Receptor antagonist), WAY-100635 (6μg/rat, selective 5-HT1A Receptor antagonist), SB-224289 (5μg/rat, selective 5-HT1B Receptor antagonist), BRL-15572 (4μg/rat, selective 5-HT1D Receptor antagonist) and SB-659551 (6μg/rat, selective 5-HT5A Receptor antagonist), but not naloxone (50μg/rat, non-selective opioid Receptor antagonist), were able to prevent mangiferin-induced anti-allodynic effect. These data suggest that the anti-allodynic effect induced by mangiferin is mediated at least in part by the serotoninergic system, involving the activation of 5-HT1A/1B/1D/5A Receptors, as well as the nitric oxide-cyclic GMP-ATP-sensitive K+ channels pathway, but not by the opioidergic system, in the SNL model of neuropathic pain in rats.
Guadalupe García-alcocer - One of the best experts on this subject based on the ideXlab platform.
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Expression of hippocampal serotonin Receptors 5-HT2C and 5-HT5A in a rat model of diet-induced obesity supplemented with tryptophan.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2015Co-Authors: Sarahi Lopez‐esparza, Laura C Berumen, Ricardo Miledi, Karla Padilla, Guadalupe García-alcocerAbstract:Food intake regulation is a complex mechanism that involves endogenous substances and central nervous system structures like hypothalamus or even hippocampus. The neurotransmitter serotonin is distinguished as food intake mediator; within its multiples Receptors, the 5-HT2C type is characterized by its inhibitory appetite action but there is no information about 5-HT5A Receptors involvement in obesity disease. It is also unknown if there are any changes in the Receptors expression in rats hippocampus with induced obesity during development through a high energy diet (HED) supplemented with tryptophan (W). To appreciate the Receptors expression pattern in the hippocampus, obesity was induced to young Sprague Dawley rats through a HED and supplemented with W. Immunocytochemical and western blot techniques were used to study the Receptor distribution and quantify the protein expression. The rats with HED diet developed obesity until week 13 of treatment. The 5-HT2C Receptor expression decreased in CA1, CA2, CA3 and DG of HED group; and also in CA2, CA3 and DG for HEDW group. The 5-HT5A Receptor expression only decreased in DG for HED group. Variations of the two serotonin Receptors subtypes support their potential role in obesity.
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Serotonin Receptor 5-HT5A in rat hippocampus decrease by leptin treatment.
Neuroscience letters, 2010Co-Authors: Guadalupe García-alcocer, Laura C Berumen, Angelina Rodríguez, Paulina Moreno-layseca, Jesica Escobar, Ricardo MilediAbstract:Hydroxytryptamine (5-HT) is involved in a variety of different physiological processes and behaviors through the activation of equally diverse Receptors subtypes. In this work we studied the changes on the expression of 5-HT5A Receptors in rat hippocampus induced by leptin, an adipocyte-derived hor- mone that has been reported to participate in the modulation of food intake and in adult hippocampal neurogenesis. To study the effect of leptin on the 5-HT5A Receptor gene expression a qRT-PCR was used and the distribution of those Receptors in the hippocampus was visualized by immunohistochemistry. Rats were separated in four groups: control (untreated rats), leptin-treated, serotonin-treated and lep- tin + serotonin treated. The results showed that even though the 5-HT5A gene expression did not change in the hippocampus of any of the treated groups, in the rats treated with leptin and serotonin, the specific immunostaining for the 5-HT5A serotonin Receptor decreased significantly in the dentate gyrus. © 2010 Elsevier Ireland Ltd. All rights reserved.
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Developmental expression of 5-HT5A Receptor mRNA in the rat brain
Neuroscience letters, 2005Co-Authors: Guadalupe García-alcocer, Gabriela Sarabia-altamirano, Ataúlfo Martínez-torres, Ricardo MilediAbstract:Abstract In the central nervous system, serotonin (5-HT) may function as a mitogen as well as a neurotransmitter; and its early appearance suggests a potential role in development. The present experiments were done to determine the localization of the mRNA coding for the 5-HT 5A Receptor during development of the rat brain. 5-HT 5A gene transcription was assessed by in situ hybridization, from E18 and during postnatal (PN) development. An intense signal of 5-HT 5A mRNA was found in the cerebral cortex and olfactory nucleus at E18, PN0 and PN5. A sharp decrease at PN11 was followed by an increase until reaching the adult level in the cerebral cortex; whereas in the olfactory nucleus, transcription remained weak. In contrast, in the hippocampal formation the signal was weak in the CA1, CA2 and CA3 regions at E18 and PO; increased at P5 and then decreased at P11 before attaining the adult level. We conclude that the gene coding for the 5-HT 5A Receptor is already active in the embryonic rat brain and is differentially expressed during development.
