Effect of epinephrine on cAMP accumulation in cultured rat inner medullary collecting duct cells.

In a previous study we have reported the existence of alpha2- and beta-adrenoceptors in cultured rat inner medullary collecting duct (IMCD) cells. In this report, we examined the effect of epinephrine on intracellular adenosine 3',5'-cyclic monophosphate (cAMP) accumulation and evaluated whether alpha2-adrenoceptors interact with beta-receptors, vasopressin receptors, and prostaglandin (PG) E2 receptors by measuring cAMP generation. Epinephrine stimulated cAMP accumulation in a dose-dependent manner [half-maximal effective concentration (EC50) = 300 nM]. Rauwolscine (10 microM) enhanced epinephrine effects, shifting the dose-response curve for epinephrine to the left (EC50 = 120 nM); however, beta-antagonists inhibited epinephrine-induced cAMP accumulation. Epinephrine (10 microM) inhibited cAMP accumulation maximally induced by isoproterenol (10 microM); this effect was reversed by rauwolscine (10 microM). Epinephrine inhibited vasopressin (100 nM)-induced cAMP accumulation but failed to inhibit PGE2 (10 microM)-induced cAMP accumulation. We conclude that epinephrine acts as an alpha2- and beta-adrenoceptor agonist and that alpha2-adrenoceptors interact with beta-adrenoceptors and vasopressin receptors but not with PGE2 receptors on cAMP accumulation. This suggests that alpha2-adrenoceptors play a physiological role via interaction with different hormone receptors.