Abstract

These experiments were designed to characterize P2 purinergic receptor-mediated effects on renin secretion, using the rat renal cortical slice preparation. 2-Methylthio ATP (10-500 microM) and ATP (100-500 microM) stimulated renin secretion in a concentration-dependent manner and 2-methylthio ATP was the more potent. By contrast, alpha, beta-methylene ATP (0.1-500 microM) had no effect on renin secretion. This order of potency (2-methylthio ATP > ATP > alpha, beta-methylene ATP) indicates that activation 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-methylthio ATP to 2-methylthio adenosine, followed by activation of P1 purinergic receptors. In contrast, N omega-nitro-I-arginine methyl ester both antagonized the basal renin secretory rate and blocked the stimulating effects on renin secretion of 2-methylthio ATP. Because N omega-nitro-l-arginine methyl ester antagonizes the production of nitric oxide by endothelial cells, these results suggest that nitric acid stimulates basal renin secretion in this experimental preparation and that increased production of it mediates the stimulating effects on renin secretion of activation of P2y purinergic receptors.