Long-term inhibitory effect of cAMP on β-adrenoceptor acquisition and nonselective attenuation of adenylyl cyclase in hepatocytes

Abstract

Long-term effects of cAMP on the surface expression of β-adrenoceptors and adenylyl cyclase activity were investigated in primary cultures of rat hepatocytes. β-Adrenoceptor density and catecholamine-responsive adenylyl cyclase activity increased during culturing in a biphasic manner, with a plateau of 10–20 h duration occurring approximately 10 h after plating. Treatment of hepatocyte cultures with 8-bromo-cAMP during the plateau period did not affect the density of β-adrenoceptors. In contrast, addition of 8-bromo-cAMP, 8-chlorophenylthio-cAMP, forskolin or glucagon during a period of active recruitment of surface β-adrenoceptors resulted in a suppression of the acquisition of β-adrenoceptors. In both experimental situations there was a partial decrease in hormone-stimulated and basal adenylyl cyclase activity. The results suggest that cAMP exerts at least two types of long-term regulation of adenylyl cyclase in hepatocytes: a suppressive effect on β-adrenoceptor acquisition, and a partial, nonselective decrease in adenylyl cyclase activity not involving β-adrenoceptor down-regulation.