Agonist-stimulated [S-35]GTP gamma S binding by alpha(2)-adrenoceptors was
examined in rat brain by autoradiography. Epinephrine, norepinephrine, dexm
edetomidine and brimonidine stimulated [S-35]GTP gamma S binding in a dose-
dependent manner. Agonist-stimulated binding was blocked by the specific al
pha(2)-adrenoceptor antagonist (1,4-benzodioxan-2-methoxy-2-yl)-2-imidazoli
ne hydrochloride (RX821002). Each alpha(2)-adrenoceptor agonist stimulated
[S-35]GTP gamma S binding in the same brain regions, corresponding to alpha
(2)-adrenoceptor distribution determined by [I-125]para-iodoclonidine autor
adiography. The order of antagonist potency (RX821002 > idazoxan > rauwolsc
ine > phentolamine > prazosin), and weak inhibition by propranolol and sele
ctive serotonin antagonists, indicate that epinephrine-stimulated [S-35]GTP
gamma S binding is mediated primarily by alpha(2)-adrenoceptors. Several a
ntagonists increased [S-35]GTP gamma S binding at very high concentrations,
and this effect had anatomic and pharmacologic characteristics of binding
mediated by 5-HT1A receptors. These studies demonstrate functional linkage
of alpha(2)-adrenoceptors to G proteins in tissue sections, thus providing
data on neuroanatomic localization and a means to examine drug specificity
at alpha(2)-adrenoceptors in different brain regions. (C) 2000 Elsevier Sci
ence B.V. All rights reserved.