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-CPT-cAMP) to hepatocytes at the time of plating enhanced the acquisition of beta-adrenoceptors that occurs spontaneously upon culturing as primary monolayers. This effect was partially suppressed by the phosphodiesterase inhibitor isobutyl methylxanthine, and was mimicked by 8-bromo-AMP, 8-bromo-adenosine, and the adenosine kinase inhibitor 5'-amino-5'-deoxyadenosine. Agents that elevated the intracellular level of cAMP, such as glucagon and forskolin, and Sp-8-bromo-adenosine 3',5'-monophosphorothioate (Sp-8-bromo-cAMPS), a cAMP analogue that is resistant towards metabolic breakdown, did not significantly enhance beta-adrenoceptor expression when used alone, but glucagon enhanced the effect of 8-bromo-adenosine. 8-bromo-cAMP and 8-bromo-adenosine decreased cellular ATP-levels. These observations suggest that the enhanced beta-adrenoceptor acquisition was mediated mainly through the action of metabolites of 8-bromo-cAMP and 8-CPT-cAMP, although there may be a cAMP-mediated component in the effect. Several mechanisms, including depletion of ATP, are probably involved, and might affect beta-adrenoceptor degradation.