Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rat has proven to be a valuable preclinical model for characterizing effects of psychotrophic drugs and for identifying new psychotherapeutic agents in pharmacological screens. However, substantial differences have been described between the rat and human brain in regard to the neuroanatomical distribution of some drug and neurotransmitter receptor binding sites. To assess the utility of the rat as a model for the neuroanatomical topography of 5-HT1A and type 1 benzodiazepine (BDZ) receptors in humans, the distribution of binding sites for 3H-8-OH-DPAT (5-HT1A agonist) and 3H-zolpidem (type 1 BDZ agonist) was compared with autoradiography in select regions of the rat and human brain. Concordance in the binding patterns for the two ligands was observed in several brain regions for the two species. However, substantial differences were also found in the topography of binding sites for the ligands in the rat and human brain. High 3H-8-OH-DPAT binding was seen in the dorsal raphe nucleus and hippocampal formation in both the rat and human brain. However, species differences were observed in the relative distribution of ligand binding among hippocampal subregions. In the cerebral cortex, the laminar distribution of 3H-8-OH-DPAT binding sites was notably different for rats and humans. In humans, outer cortical layers were most densely labeled with 3H-8-OH-DPAT, whereas in the rat cortex, the highest binding was in the inner layers. A striking difference between rats and humans was observed for 3H-8-OH-DPAT binding in the lateral septal nucleus, which was densely labeled in the rat but weakly labeled in humans. Substantial differences between rats and humans were also observed for 3H-zolpidem binding. In the rat brain, high densities of binding sites were found in the medial septum, inferior colliculus, and substantia nigra reticulata. These regions showed very low 3H-zolpidem binding in the human brain. Intermediate binding was seen in the rat cerebral cortex, and low binding was found in the hippocampus. By contrast, in humans, cerebral cortical regions were the most densely labeled of all regions studied, and certain hippocampal subregions exhibited relatively high binding. The striking neuroanatomical differences in 3H-8-OH-DPAT and 3H-zolpidem binding observed between rats and humans suggest that different functional consequences may be produced within specific brain regions after administration of drugs that influence 5-HT1A and type 1 BZD receptors.
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PMID:Species differences in regional patterns of 3H-8-OH-DPAT and 3H-zolpidem binding in the rat and human brain. 963 27

This study investigated the neurodevelopmental basis of schizophrenia by examining an early transient population of serotonin-1A (5-HT1A) receptors using quantitative [3H]8-OH-DPAT autoradiography on sections of frozen postmortem cerebellum. Production of an ontogenetic map showed that human neonatal cerebellum acquired dense 5-HT1A receptors, most of which were eliminated by early childhood. Autoradiographic measurements on cerebellar vermis from 16 control adult subjects confirmed sparse 5-HT1A receptor binding. The data show a persistence of some vermal 5-HT1A receptors in brains from 19 adults with chronic schizophrenia in whom there may have been a slowed or arrested postnatal regression of vermal 5-HT1A receptors. Alternatively, some 5-HT1A receptors may have been re-expressed prior to, or subsequent to, the onset of the disease symptoms. The findings are not obviously explained by drug treatment and there are no data to explain how neuroleptics might promote expression of cerebellar 5-HT1A receptors. We propose that the study has identified a neurotransmitter receptor population which, in schizophrenia, undergoes misdirected reshaping during brain development. The findings support neurodevelopmental hypotheses of the disease.
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PMID:Abnormal persistence of cerebellar serotonin-1A receptors in schizophrenia suggests failure to regress in neonates. 966 Jan 9

7-Methoxy-6-[3-[4-(2-methoxyphenyl)piperazin-1-yl]propoxy]-3,4-dim ethyl-2H-1-benzopyran-2-one hydro-chloride (KA-672), structurally related to naturally occurring coumarins, has been described as a potential drug for enhancing cognitive functions. However, a detailed characterization of the pharmacological profile of KA-672 in vivo is still lacking. Quantitative neurotransmitter receptor autoradiography was used as a tool to screen for KA-672-induced changes in a number of transmitter receptors including cholinergic, noradrenergic, glutamatergic, GABAergic, and serotonergic subtypes throughout the brain. Two hours following treatment of mice with 1 mg/kg KA-672 per os, slight increases of nicotinic and M1-muscarinic cholinergic receptor binding, of alpha2-and beta-adrenoceptor as well as 5-HT1A receptors in various cerebral cortical regions were observed, whereas 5-HT2A binding sites were strikingly increased throughout the brain following KA-672 treatment. In contrast, (+/-)-alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor binding was significantly decreased in some cortical regions after drug treatment. No effects of KA-672 treatment on N-methyl-D-aspartate, kainate, GABA(A) and benzodiazepine receptor as well as M2-muscarinic cholinergic and high-affinity choline uptake binding were observed. As interactions between the cholinergic, noradrenergic and serotonergic neurotransmission have been stressed to play important roles in realizing learning and memory events, the cognition-enhancing effects of KA-672 may be due to this complex in vivo pharmacological profile of KA-672.
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PMID:Acute effect of KA-672, a putative cognitive enhancer, on neurotransmitter receptor binding in mouse brain. 1054 21

We have monitored the ligand binding of the bovine hippocampal 5-HT1A receptor following treatment with the sterol-binding antifungal antibiotic nystatin. Nystatin considerably inhibits the specific binding of the antagonist to 5-HT1A receptors in a concentration-dependent manner. However, the specific agonist binding does not show significant changes. Fluorescence polarization measurements of membrane probes incorporated at different locations in the membrane revealed a substantial decrease in the membrane order in the interior of the bilayer. Experiments with cholesterol-depleted membranes indicate that the action of nystatin is mediated through membrane cholesterol. These results represent the first report on the effect of a cholesterol-perturbing agent on the ligand-binding activity of this important neurotransmitter receptor.
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PMID:The sterol-binding antibiotic nystatin differentially modulates ligand binding of the bovine hippocampal serotonin1A receptor. 1521 65

The laminar distributions of 16 neurotransmitter receptor binding sites were analysed in visual cortical areas V1-V3 by quantitative in vitro receptor autoradiography. For each receptor (glutamatergic: AMPA, kainate, NMDA; cholinergic: M1, M2, M3, nicotinic; GABAergic: GABAA, GABAB, benzodiazepine binding-sites; adrenergic: alpha1, alpha2; serotoninergic: 5-HT1A, 5-HT2; dopaminergic: D1; Adenosine: A1), density profiles extracted perpendicular to the cortical surface were compared to cyto- and myeloarchitectonic profiles sampled at corresponding cortical sites. When testing for differences in laminar distribution patterns, all receptor-density profiles differed significantly from the cyto- and myeloarchitectonic ones. These results indicate that receptor distribution is an independent feature of the cortical architecture not predictable by densities of cell bodies or myelinated fibres. Receptor co-distribution was studied by cluster analyses, revealing several groups of receptors, which showed similar laminar distribution patterns across all analysed areas (V1-V3). Other receptors were co-distributed in extrastriate but not primary visual cortex. Finally, some receptors were not co-distributed with any of the analysed other ones. A comparison of the laminar patterns of receptor binding sites in the human visual cortex with those reported for non-human primates and other mammals showed that the laminar distributions of cholinergic and glutamatergic receptors seem largely preserved, while serotoninergic and adrenergic receptors appear to be more variable between different species.
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PMID:Laminar distribution and co-distribution of neurotransmitter receptors in early human visual cortex. 1782 18


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