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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010762:Phosphorylase a / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D000242:Cyclic AMP; D010762:Phosphorylase a; D002118:Calcium