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Titolo:
Calcium changes induced by presynaptic 5-hydroxytryptamine-3 serotonin receptors on isolated terminals from various regions of the rat brain
Autore:
Nayak, SV; Ronde, P; Spier, AD; Lummis, SCR; Nichols, RA;
Indirizzi:
Allegheny Univ Hlth Sci, Dept Pharmacol, Philadelphia, PA 19129 USA Allegheny Univ Hlth Sci Philadelphia PA USA 19129 ladelphia, PA 19129 USA Allegheny Univ Hlth Sci, Dept Neurobiol & Anat, Philadelphia, PA 19129 USAAllegheny Univ Hlth Sci Philadelphia PA USA 19129 ladelphia, PA 19129 USA MRC, Mol Biol Lab, Div Neurobiol, Cambridge CB2 2QH, England MRC Cambridge England CB2 2QH Div Neurobiol, Cambridge CB2 2QH, England Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England Univ Cambridge Cambridge England CB2 1QW hem, Cambridge CB2 1QW, England
Titolo Testata:
NEUROSCIENCE
fascicolo: 1, volume: 91, anno: 1999,
pagine: 107 - 117
SICI:
0306-4522(1999)91:1<107:CCIBP5>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
NUCLEUS-TRACTUS-SOLITARIUS; GATED ION-CHANNEL; 5-HT3 RECEPTORS; CEREBRAL-CORTEX; NERVE-TERMINALS; RELEASE; ANTAGONISTS; LIGAND; IDENTIFICATION; ACETYLCHOLINE;
Keywords:
5-HT3 receptors; synaptosomes; calcium; confocal imaging;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Nichols, RA Allegheny Univ Hlth Sci, Dept Pharmacol, Philadelphia, PA 19129 USA Allegheny Univ Hlth Sci Philadelphia PA USA 19129 A 19129 USA
Citazione:
S.V. Nayak et al., "Calcium changes induced by presynaptic 5-hydroxytryptamine-3 serotonin receptors on isolated terminals from various regions of the rat brain", NEUROSCIENC, 91(1), 1999, pp. 107-117

Abstract

The serotonin 5-hydroxytryptamine-3 receptor is a ligand-gated ion channelthat is distributed widely in the nervous system. Within the CNS, a significant portion of the 5-hydroxytryptamine-3 receptors appears to be present on presynaptic nerve terminals and, using an imaging approach, it was shownpreviously that presynaptic 5-hydroxytryptamine-3 receptors on individual isolated nerve terminals (synaptosomes) from rat corpus striatum display a distinctive set of properties-slow onset, little desensitization and high apparent permeability for Ca2+-when compared to those observed for 5-hydroxytryptamine-3 receptors localized at postsynaptic sites on neuronal cell bodies. To consider whether their characteristic nature is a common feature ofpresynaptic 5-hydroxytryptamine-3 receptors across the brain, we used confocal microscopy to measure changes in intracellular Ca2+ concentration resulting from 5-hydroxytryptamine 3 agonist-induced responses in synaptosomes from representative rat brain regions, ranging in expression of overall levels of 5-hydroxytryptamine-3 receptors from relatively low (cerebellum) to intermediate (corpus striatum and hippocampus) to high (amygdala). Application of 100 nM m-chlorophenyl biguanide, a specific 5-hydroxytryptamine-3 receptor agonist, induced changes in relative intracellular Ca2+ concentration in subsets of synaptosomes from the corpus striatum (similar to 6% of total), hippocampus (similar to 3% of total), amygdala (similar to 30% of total) and cerebellum (similar to 32% of total). In order to assure the viability of the synaptosomes that did not respond to 5-hydroxytryptamine-3 agonist stimulation, KCI (45 mM) was subsequently added to depolarize the same population of synaptosomes, and increases in intracellular Ca2+ concentrationwere then seen in 80-90% of the synaptosomes from all four regions. The kinetics of the intra synaptosomal Ca2+ changes produced by K+-evoked depolarization were similar in all regions, showing a rapid rise to a peak followed by an apparent plateau phase. In contrast, the changes in intracellular Ca concentration evoked by m-chlorophenyl biguanide displayed substantially slower kinetics, similar to previous findings, but which varied among responding synaptosomes from one region to another. In particular, in-chlorophenyl biguanide-induced changes were notably slower in synaptosomes from the amygdala (rise time constant, tau = 25 s), when compared to responses in synaptosomes from other regions (striatum, tau = 12 s; hippocampus, tau = 9.6 s; cerebellum, tau = 7 s). To independently demonstrate the presence of 5-hydroxytryptamine-3 receptors on nerve terminals in the various regions using a molecular approach, we double-immunostained the synaptosomes for the 5-hydroxytryptamine-3 receptor and the synaptic vesicle protein synaptophysin, using, respectively, a polyclonal antibody raised against an N-terminal peptide of the 5-hydroxytryptamine-3 receptor and a monoclonal anti-synaptophysin antibody, and observed 5-hydroxytryptamine-3 receptors in varying subsets of the synaptosomes from each region, providing direct support for theresults obtained in our functional experiments. These results suggest that the distinctive properties of presynaptic 5-hydroxytryptamine-3 receptors are found throughout the brain, with evident differences in the kinetics of the responses to agonist stimulation observed across the brain regions studied. As expected, the proportion of the synaptosomal population that responded on application of 5-hydroxytryptamine-3 agonist varied in preparations from one region to another; however, the presence of a relatively high proportion of presynaptic 5-hydroxytryptamine-3 receptors in the cerebellum contrasts with previous binding studies demonstrating a relatively low overall density of 5-hydroxytryptamine-3 receptors in this region. We hypothesize that presynaptic 5-hydroxytryptamine-3 receptors present on nerve terminals regulate the functioning of select synapses throughout the rat brain. (C) 1999 IBRO. Published by Elsevier Science Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 22:59:53