alpha(2)-adrenoceptor-stimulated GTP gamma S binding in rat brain: an autoradiographic study

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.