α2-Adrenoceptor-stimulated GTPγS binding in rat brain: an autoradiographic study

Abstract Agonist-stimulated [ 35 S]GTPγS binding by α 2 -adrenoceptors was examined in rat brain by autoradiography. Epinephrine, norepinephrine, dexmedetomidine and brimonidine stimulated [ 35 S]GTPγS binding in a dose-dependent manner. Agonist-stimulated binding was blocked by the specific α 2 -adrenoceptor antagonist (1,4-benzodioxan-2-methoxy-2-yl)-2-imidazoline hydrochloride (RX821002). Each α 2 -adrenoceptor agonist stimulated [ 35 S]GTPγS binding in the same brain regions, corresponding to α 2 -adrenoceptor distribution determined by [ 125 I]para-iodoclonidine autoradiography. The order of antagonist potency (RX821002>idazoxan>rauwolscine>phentolamine>prazosin), and weak inhibition by propranolol and selective serotonin antagonists, indicate that epinephrine-stimulated [ 35 S]GTPγS binding is mediated primarily by α 2 -adrenoceptors. Several antagonists increased [ 35 S]GTPγS binding at very high concentrations, and this effect had anatomic and pharmacologic characteristics of binding mediated by 5-HT 1A receptors. These studies demonstrate functional linkage of α 2 -adrenoceptors to G proteins in tissue sections, thus providing data on neuroanatomic localization and a means to examine drug specificity at α 2 -adrenoceptors in different brain regions.