Adenosine a agonist inhibits forskolin-induced renin secretion by cultured renal cortical cells

A number of studies have indicated that adenosine (Ado) exerts a physiological role in the control of renin secretion (RS). The present study was conducted to examine the utility of N6-endonorbornyl Ado (ENBA) in studies of the mechanism of Ado-induced inhibition of RS. ENBA is a stable, highly selective agonist at Ado receptors (AdoR) of the Aj subtype. Rat renal cortical cells were prepared by enzymatic dispersion using collagenase and elastase, followed by density gradient separation (Percoll) and selective plating to obtain a preparation enriched in cells that secrete renin. Primary cultures of these cells were studied 20 - 36 hours after plating. Cellular renin content and RS into culture medium (expressed as fractional RS; % of total) was assessed by RIA of angiotensin I generated by samples in the presence of excess renin substrate. Basal RS, 0.8±0.1 % hr ' (mean ±S.E; n=6) was increased by both forskolin (20 ]M) and calmidazolium (10 U.M) treatments. ENBA (1 jlM) inhibited forskolininduced RS by ca. 60%, from 2.1±0.1 to 1.3±0.1% hr -', but did not change basal RS significantly. In one primary preparation, a selective AI AdoR antagonist, xanthine amine congener (5 UM), did not change basal RS but abolished the inhibitory effect of ENBA on forskolin-induced renin secretion. The results support other in vitro and in vivo findings that inhibition of RS by Ado is likely attributable to its stimulation of A₁AdoR and are consistent with findings in other cell types that agonist activity at the A₁AdoR may oppose effects that are stimulated by cyclic AMP.