FORSKOLIN AS AN ACTIVATOR OF CYCLIC-AMP ACCUMULATION AND LIPOLYSIS IN RAT ADIPOCYTES

Abstract

Forskolin [from Coleus forskohlii] increased cAMP accumulation in isolated adipocytes and markedly potentiated the elevation of cAMP due to isoproterenol. In adipocyte membranes, forskolin stimulated adenylate cyclase activity at concentrations of .gtoreq. 0.1 .mu.M. Forskolin did not affect the EC50 [median effective concentration] for activation of adenylate cyclase but did not increase the maximal effect of isoproterenol. Neither the soluble nor particulate low-Km cAMP phosphodiesterase activity was affected by forskolin. Low concentrations of forskolin (0.1-1.0 .mu.M) which significantly elevated cAMP levels did not increase lipolysis, whereas similar increases in cAMP levels due to isoproterenol elevated lipolysis. Forskolin did not inhibit the activation of triacylglycerol lipase by cAMP-dependent protein kinase or the subsequent hydrolysis of triacylglycerol. Higher concentrations of forskolin (10-100 .mu.M) increased lipolysis. Both the increased cAMP production and lipolysis due to forskolin were inhibited by the antilipolytic agents insulin and N6-(phenylisopropyl)adenosine. Hypothyroidism reduced the ability of forskolin to stimulate cAMP-production and lipolysis. Evidently forskolin increases cAMP production in adipocytes through an activation of adenylate cyclase. Lipolysis is activated by forskolin, but at higher concentrations of total cAMP than for catecholamines.