Regulation of renal cellular cAMP levels by prostaglandins and α2-adrenoceptors: Microdissection studies

Abstract

Previous studies in our laboratory demonstrated that α2-adrenoceptor activation reversed arachidonic acid induced diuresis in the rat. However, the site of action was not elucidated. Since prostaglandin E2 is the predominant prostaglandin metabolite of arachidonic acid, we studied the effect of renal α2-adrenoceptor stimulation on prostaglandin E2 (PGE2) induced cAMP formation. The study was done in intact single nephron segments and glomeruli. All incubations were done in the presence of 1-methyl-3-isobutylxanthine (phosphodiesterase inhibitor) and propranolol at 37°C for two minutes. PGE2 increased cellular cAMP levels in the thin descending limb of Henle (tDL), cortical collecting tubule (CCT) and glomerulus. Alpha2-adrenoceptors were activated with varying concentrations of epinephrine (E). In the tDL, α2-adrenoceptor activation with E (5 x 10-6M to 5 x 10-5M) suppressed (p < 0.05) PGE2 stimulated cAMP production by 35%. This suppression by E was inhibited by 5 x 10-6M yohimbine but not by 5 x 10-6M prazosin confirming α2-adrenoceptor mediation of the effects of E. Conversely, in the CCT and glomerulus, E had no effect on PGE2-stimulated increases in cellular cAMP levels. Thus, the capacity of α2-adrenoceptors to inhibit PGE2-stimulated adenylate cyclase is anatomic site-specific. This effect of α2-adrenoceptors on cAMP in the tDL may explain, at least in part, the effect of α2-adrenoceptors on arachidonic acid induced diuresis in the rat.