Desensitization effect of in vivo treatment with metaproterenol on beta(1), beta(2) and beta(3)-adrenergic responsiveness in rat adipocytes

The desensitization process of P-adrenergic system was assessed by in vivo administration to 7-week old rats of a mixed beta-agonist, metaproterenol (3,5-dyhydroxyphenyl-N-isopropyl-amine-beta sulphate; T1/2=6 hours), (2 mg/kg/d) in treatments of 12 hours, 2 days and 10 days. The in vitro lipolytic effect of selective beta-adrenergic agonists, dobutamine, salbutamol and BRL 37344, as well as plasma free fatty acid concentrations were measured in treated and control animals given vehicle. Different times of exposure to a beta-agonist induced a loss of responsiveness on lipolytic response mediated by beta(1) and beta(2)-adrenoceptors, as demonstrated by decreased affinity and intrinsic activity (maximal effect) of dobutamine and salbutamol. In contrast, no changes were found in B-3-mediated lipolysis. These observations suggest that beta(1), beta(2) and beta(3)-adrenoceptors follow different regulatory patterns. Lack of beta 3-adrenoceptor desensitization may have important physiological and therapeutic consequences in the treatment of diseases such as obesity and heart failure.