LONG-TERM INHIBITORY EFFECT OF CAMP ON BETA-ADRENOCEPTOR ACQUISITION AND NONSELECTIVE ATTENUATION OF ADENYLYL-CYCLASE IN HEPATOCYTES

Long-term effects of cAMP on the surface expression of beta-adrenocept ors and adenylyl cyclase activity were investigated in primary culture s of rat hepatocytes. Beta-Adrenoceptor density and catecholamine-resp onsive adenylyl cyclase activity increased during culturing in a bipha sic manner, with a plateau of 10-20 h duration occurring approximately 10 h after plating. Treatment of hepatocyte cultures with 8-bromo-cAM P during the plateau period did not affect the density of beta-adrenoc eptors. In contrast, addition of 8-bromo-cAMP, 8-chlorophenylthio-cAMP , forskolin or glucagon during a period of active recruitment of surfa ce beta-adrenoceptors resulted in a suppression of the acquisition of beta-adrenoceptors. In both experimental situations there was a partia l decrease in hormone-stimulated and basal adenylyl cyclase activity. The results suggest that cAMP exerts at least two types of long-term r egulation of adenylyl cyclase in hepatocytes: a suppressive effect on beta-adrenoceptor acquisition, and a partial, nonselective decrease in adenylyl cyclase activity not involving beta-adrenoceptor down-regula tion.