DIFFERENT SENSITIVITY OF ALPHA(2)A-C10 AND ALPHA(2)C-C4 RECEPTOR SUBTYPES IN COUPLING TO INHIBITION OF CAMP ACCUMULATION

Two human alpha(2)-adrenergic receptor subtypes, alpha(2)A-C10 and alp ha(2)C-C4, were compared with respect to their ability to inhibit stim ulated cAMP-production. The inhibition was transduced with about one o rder of magnitude higher sensitivity in the alpha(2)C-C4 subtype than in the alpha(2)A-C10 subtype. The phorbol ester, TPA, known to desensi tize alpha(2)-adrenergic receptor function, possible through phosphory lation of G(i), almost completely abolished the inhibition of cAMP-pro duction in the alpha(2)C-C4 subtype, while only a partial effect was s een in the alpha(2)A-C10 subtype. These results suggest that the recep tor subtypes differ with respect to their coupling efficiency to adeny lyl cyclase. (C) 1994 Academic Press, Inc.