Regulatory states of adenylate cyclase in RL-PR-C cloned rat hepatocytes.

The adenylate cyclase of cloned differentiated rat hepatocytes (RL-PR-C) is regulated by cholera toxin, guanine nucleotides and fluoride. The activation of hepatic adenylate cyclase by cholera toxin was additive with that by GTP and synergistic with that by epinephrine. In contrast, when membranes were exposed to cholera toxin in the presence of Gpp(NH)p or fluoride, the response was the same as to these agents in the absence of cholera toxin. Cholera toxin-activated membranes were responsiveness only to epinephrine and GTP, while fluoride-activated membranes responded somewhat to all other agents, and Gpp(NH)p-activated membranes responded to no other agents. These data suggest that responsiveness of hepatic adenylate cyclase to cholera toxin, fluoride and Gpp(NH)p cannot be expressed simultaneously. A model is presented to explain these observations which invokes multiple states of adenylate cyclase, each being sensitive to, or brought about by, a different regulatory agent.