Nitrergic and purinergic regulation of the rat pylorus

The role of nitric oxide (NO) and ATP in the regulation of nonadrenergic, n oncholinergic (NANC) inhibitory transmission in the pylorus remains unclear . In the presence of atropine and guanethidine, electric field stimulation induced NANC relaxations in a frequency-dependent manner (1-20 Hz) in the r at pylorus. NANC relaxations were significantly inhibited by N-G-nitro-L-ar ginine methyl ester (L-NAME; 10(-4) M). P-2X purinoceptor antagonist pyrido xal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 3 x 10(-5) M) and P -2Y purinoceptor antagonist reactive blue 2 (2 x 10(-5) M) had no effect on NANC relaxations. However, the combined administration of L-NAME and PPADS , but not reactive blue 2, evoked greater inhibitory effects on NANC relaxa tion than that evoked by L-NAME alone. alpha-Chymotrypsin and vasoactive in testinal polypeptide antagonist did not affect NANC relaxations. ATP (10(-5 ) -10(-3) M) and P-2X purinoceptor agonist alpha,beta-methyleneadenosine 5' -triphosphate (10(-7) -10(-5) M), but not P-2Y purinoceptor agonist 2-methy l-thioadenosine 5'-triphosphate (10(-7) -10(-5) M), induced muscle relaxati ons in a dose-dependent manner, and relaxations were significantly reduced by PPADS and unaffected by TTX. These studies suggest that NO and ATP act i n concert to mediate NANC relaxation of the rat pylorus. ATP-induced relaxa tion appears to be mediated by P-2X purinoceptors located on smooth muscle cells.