CHARACTERIZATION OF TWO 5-HYDROXYTRYPTAMINE RECEPTORS COUPLED TO ADENYLATE CYCLASE IN GUINEA PIG HIPPOCAMPUS.
Item
-
Title
-
CHARACTERIZATION OF TWO 5-HYDROXYTRYPTAMINE RECEPTORS COUPLED TO ADENYLATE CYCLASE IN GUINEA PIG HIPPOCAMPUS.
-
Identifier
-
AAI8508735
-
identifier
-
8508735
-
Creator
-
SHENKER, ANDREW.
-
Contributor
-
Jack Peter Green
-
Date
-
1985
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Health Sciences, Pharmacology
-
Abstract
-
The development of appropriate assay conditions has allowed quantitative pharmacological characterization of 5-HT-stimulated adenylate cyclase activity in membranes of adult guinea pig hippocampus. Stimulation of adenylate cyclase activity by 5-HT is concentration-dependent, GTP-dependent, and additive to responses elicited by dopamine, (-)isoproterenol and histamine, indicating that distinct 5-HT receptors mediate the effect.;Treatment of guinea pigs with reserpine, which depletes brain 5-HT, selectively increases the responsiveness of hippocampal adenylate cyclase to 5-HT. Exposure of hippocampal membranes to 5-HT in vitro causes decreased responsiveness to 5-HT. Maximal stimulation by 5-HT may be related to the proportions of coupled and desensitized 5-HT receptors in the preparation.;Characterization of 5-HT-stimulated adenylate cyclase activity reveals that two, pharmacologically distinct 5-HT receptors mediate the response. The two receptors were characterized with selected agonists and antagonists and with the aid of computerized curve-fitting procedures. Neither receptor may be classified as the 5-HT(,2) or as the "peripheral neuronal" (5-HT(,3)) type. 5-HT is only about 10-fold more potent in eliciting response through one cyclase-linked receptor (R(,H)) than the other (R(,L)). The two receptors are best discriminated by the agonists 5-carboxamidotryptamine and 8-hydroxy-2(di-n-propylamino)-tetralin and by the antagonist spiperone, all of which are selective for R(,H). Spiperone acts as a simple competitive antagonist at R(,H), with a dissociation constant of 20 nM. The characteristics of R(,H) suggest that it is the functional correlate of the 5-HT(,1A) binding site in brain; this receptor may mediate some of the behavioral and electrophysiological effects of 5-HT in mammals. The atypical anxiolytic buspirone is a potent partial agonist at R(,H), a finding that may be useful in understanding the pharmacological and therapeutic effects of this drug.;R(,L) probably does not correspond to a known 5-HT binding site, but it may be homologous to receptors that mediate 5-HT-stimulated adenylate cyclase activity in other systems, especially in infant rat colliculi.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
-
Program
-
Biomedical Sciences
