PHARMACOLOGICAL ANALYSIS OF DOPAMINE STIMULATION OF [S-35] GTP-GAMMA-S BINDING VIA HUMAN D-2SHORT AND D-2LONG DOPAMINE-RECEPTORS EXPRESSED IN RECOMBINANT CELLS

Citation
B. Gardner et al., PHARMACOLOGICAL ANALYSIS OF DOPAMINE STIMULATION OF [S-35] GTP-GAMMA-S BINDING VIA HUMAN D-2SHORT AND D-2LONG DOPAMINE-RECEPTORS EXPRESSED IN RECOMBINANT CELLS, British Journal of Pharmacology, 118(6), 1996, pp. 1544-1550
Citations number
34
Categorie Soggetti
Pharmacology & Pharmacy",Biology
ISSN journal
00071188
Volume
118
Issue
6
Year of publication
1996
Pages
1544 - 1550
Database
ISI
SICI code
0007-1188(1996)118:6<1544:PAODSO>2.0.ZU;2-V
Abstract
1 The activation of G-proteins by agonist-occupied D-2 or D-3 dopamine receptors in membranes from recombinant cells expressing the cloned r eceptors has been analysed by a [S-35]-guanosine 5'-[gamma-thio] triph osphate ([S-35]-GTP gamma S) binding assay. 2 The rate of [S-35]-GTP g amma S binding was increased by dopamine in a dose-dependent manner in membranes from CHO cells stably expressing either the D-2short or D-2 long dopamine receptor. 3 The dopamine-induced stimulation of [S-35]-G TP gamma S binding could be inhibited by a range of antagonists. Affin ities for antagonists derived from the inhibition of the dopamine stim ulation of [S-35]- GTP gamma S binding correlated very well with affin ities derived from radioligand binding studies. 4 When the maximum [S- 35]-GTP gamma S binding responses stimulated by dopamine acting at dif ferent receptor subtypes were compared, there was a tendency for the s timulation via the D-2short receptor to be greater than via the D-2lon g receptor and for the stimulation via the D-3 dopamine receptor to be less than for either D-2 receptor. These differences in maximal respo nse were also seen when the inhibitory effects of dopamine on adenylyl cyclase via the three receptor subtypes were compared. 5 The stimulat ion of [S-35]-GTP gamma S binding by dopamine in membranes from recomb inant cells therefore provides an excellent system for studying the mo lecular nature of agonism and the receptor/G-protein interactions for these receptors.