EFFECT OF EPINEPHRINE ON CAMP ACCUMULATION IN CULTURED RAT INNER MEDULLARY COLLECTING DUCT CELLS

In a previous study we have reported the existence of alpha(2)- and be ta-adrenoceptors in cultured rat inner medullary collecting duct (IMCD ) cells. In this report, we examined the effect of epinephrine on intr acellular adenosine 3',5'-cyclic monophosphate (cAMP) accumulation and evaluated whether alpha(2)-adrenoceptors interact with beta-receptors , vasopressin receptors, and prostaglandin (PG) E(2) receptors by meas uring cAMP generation. Epinephrine stimulated cAMP accumulation in a d ose-dependent manner [half-maximal effective concentration (EC(50)) = 300 nM]. Rauwolscine (10 mu M) enhanced epinephrine effects, shifting the dose-response curve for epinephrine to the left (EC(50) = 120 nM); however, beta-antagonists inhibited epinephrine-induced cAMP accumula tion. Epinephrine (10 mu M) inhibited cAMP accumulation maximally indu ced by isoproterenol (10 mu M); this effect was reversed by rauwolscin e (10 mu M). Epinephrine inhibited vasopressin (100 nM)-induced cAMP a ccumulation but failed to inhibit PGE(2) (10 mu M)-induced cAMP accumu lation. We conclude that epinephrine acts as an alpha(2)- and beta-adr enoceptor agonist and that alpha(2)-adrenoceptors interact with beta-a drenoceptors and vasopressin receptors but not with PGE(2) receptors o n cAMP accumulation. This suggests that alpha(2)-adrenoceptors play a physiological role via interaction with different hormone receptors.