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, metapr oterenol (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, dobu tamine, salbutamol and BRL 37344, as well as plasma free fatty acid co ncentrations were measured in treated and control animals given vehicl e. Different times of exposure to a beta-agonist induced a loss of res ponsiveness on lipolytic response mediated by beta(1) and beta(2)-adre noceptors, as demonstrated by decreased affinity and intrinsic activit y (maximal effect) of dobutamine and salbutamol. In contrast, no chang es were found in B-3-mediated lipolysis. These observations suggest th at beta(1), beta(2) and beta(3)-adrenoceptors follow different regulat ory patterns. Lack of beta 3-adrenoceptor desensitization may have imp ortant physiological and therapeutic consequences in the treatment of diseases such as obesity and heart failure.