DESENSITIZATION OF BETA-ADRENERGIC RESPONSES IN ADIPOCYTES INVOLVES RECEPTOR SUBTYPES AND CAMP-PHOSPHODIESTERASE

Acute exposure of isolated adipocytes to isoproterenol induces the des ensitization of lipolytic responses to norepinephrine and selective be ta(1)-, beta(2)- and beta(3)-adrenoceptor agonists, as well as the adr enocorticotropic hormone 1-24 fragment (ACTH). Forskolin and 8-bromo-c AMP responses are also desensitized. When lipolysis was measured in th e presence of OPC 3911 yl-4(6-(1,2-dihydro-2-oxoquinolyloxy))butyramid e}, a specific inhibitor of the cAMP phosphodiesterase of adipocytes, the desensitization of all lipolytic agents - except the beta(2)-adren oceptor agonist - was abolished. Isoproterenol induced a similar loss (35%) of both membrane beta(1)- and beta(2)-adrenoceptors and an uncou pling of beta(1)-adrenoceptors, but did not modify the weak coupling o f control beta(2)-adrenoceptors. These data suggest that isoproterenol induced (i) an activation of the cAMP phosphodiesterase, which is sol ely responsible for the desensitization of norepinephrine response as well as beta(1)- and beta(3)-adrenoceptor mediated responses and (ii) an additional desensitization of the sole beta(2)-adrenergic signaling system which suggests a subtype-selective pattern of regulating proce sses.