8-BROMO-CAMP AND 8-CPT-CAMP INCREASE THE DENSITY OF BETA-ADRENOCEPTORS IN HEPATOCYTES BY A MECHANISM NOT MIMICKING THE EFFECT OF CAMP

Addition of 8-bromo-adenosine 3',5'-cyclic monophosphate (8-bromo-cAMP ) or 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (8-CP T-cAMP) to hepatocytes at the time of plating enhanced the acquisition of beta-adrenoceptors that occurs spontaneously upon culturing as pri mary monolayers. This effect was partially suppressed by the phosphodi esterase inhibitor isobutyl methylxanthine, and was mimicked by S-brom o-AMP, B-bromo-adenosine, and the adenosine kinase inhibitor 5'-amino- 5'-deoxyadenosine. Agents that elevated the intracellular level of cAM P, such as glucagon and forskolin, and Sp-8-bromo-adenosine 3',5'-mono phosphorothioate (Sp-8-bromo-cAMPS), a cAMP analogue that is resistant towards metabolic breakdown, did not significantly enhance beta-adren oceptor expression when used alone, but glucagon enhanced the effect o f 8-bromo-adenosine. 8-Bromo-cAMP and S-bromo-adenosine decreased cell ular ATP-levels. These observations suggest that the enhanced beta-adr enoceptor acquisition was mediated mainly through the action of metabo lites of 8-bromo-cAMP and 8-CPT-cAMP, although there may be a cAMP-med iated component in the effect. Several mechanisms, including depletion of ATP, are probably involved? and might affect beta-adrenoceptor deg radation.