PURINERGIC-P(2Y) RECEPTORS STIMULATE RENIN SECRETION BY RAT RENAL CORTICAL SLICES

These experiments were designed to characterize P2 purinergic receptor -mediated effects on renin secretion, using the rat renal cortical sli ce preparation. 2-Methylthio ATP (10-500 muM) and ATP (100-500 muM) st imulated renin secretion in a concentration-dependent manner and 2-met hylthio ATP was the more potent. By contrast, alpha,beta-methylene ATP (0.1-500 muM) had no effect on renin secretion. This order of potency (2-methylthio ATP > ATP > alpha,beta-methylene ATP) indicates that ac tivation of the P2y subclass of purinergic receptors stimulates renin secretion. Theophylline did not antagonize the effect of 2-methylthio ATP, which suggests that the effect was not due to a conversion of 2-m ethylthio ATP to 2-methylthio adenosine, followed by activation of P1 purinergic receptors. In contrast, N(omega)-nitro-I-arginine methyl es ter both antagonized the basal renin secretory rate and blocked the st imulating effects on renin secretion of 2-methylthio ATP. Because N(om ega)-nitro-I-arginine methyl ester antagonizes the production of nitri c oxide by endothelial cells, these results suggest that nitric acid s timulates basal renin secretion in this experimental preparation and t hat increased production of it mediates the stimulating effects on ren in secretion of activation Of P2y purinergic receptors.