Characterisation of the alpha 1-adrenergic control of hepatic cAMP in male rats.

alpha 1-Adrenergic agonists characteristically elicit a mobilization of intracellular Ca2+ in rat liver. These agents also induced accumulation of cAMP in mature male rats (greater than 300 g body weight) and in Ca2+-depleted hepatocytes from 200 g rats although not in Ca2+-depleted cells from juvenile (less than 100 g) male rats. Comparison of these two responses revealed a similar agonist potency order in both cases, although cAMP accumulation was approximately 5-fold less sensitive to agonists. A variety of alpha-antagonists, including prazosin, phenoxybenzamine and dihydroergocryptine were equipotent as inhibitors of each response, although the alpha 1-adrenergic cAMP response was more sensitive to inhibition by WB-4101 and phentolamine. These data are discussed and a model proposed whereby in mature male rats, the same alpha 1-adrenergic receptor population becomes simultaneously coupled to two separate signal transduction mechanisms, namely Ca2+ mobilization and cAMP generation.