NITRIC-OXIDE AND PROSTAGLANDINS IN REGULATION OF ACID SECRETORY RESPONSE IN RAT STOMACH FOLLOWING INJURY

The gastric mucosa responds to taurocholate (TC) by significantly decr easing acid secretion. We examined the role of nitric oxide (NO) in th is phenomenon in comparison with endogenous prostaglandins. A rat stom ach was mounted in an ex-vivo chamber and perfused with saline, and th e potential difference, luminal pH and acid responses were measured be fore and after the application of 20 mM TC for 30 min with or without pretreatment with the NO synthase inhibitor N-G-nitro-L-arginine methy l ester (L-NAME) or the cyclooxygenase inhibitor indomethacin. Exposur e of the stomach to TC caused a reduction in potential difference, a d ecrease in acid secretion and an increase in luminal HCO3-. Pretreatme nt with L-NAME or indomethacin did not affect potential difference and HCO3- responses, but it significantly attenuated the decrease in acid secretion caused by TC. The effect of L-NAME was more potent than tha t of indomethacin, and, especially in the presence of L-NAME, acid sec retion was actually enhanced after exposure to TC. Aminoguanidine, the selective inhibitor of inducible NO synthase, did not have any signif icant effect on either parameter. This effect of L-NAME was antagonize d by the simultaneous administration of L-arginine but not by that of D-arginine, whereas the effect of indomethacin was reversed by PGE(2). Acid secretion in normal stomachs was significantly reduced by nitrop russide and PGE(2) but was not affected by either L-NAME or indomethac in. These data suggest that 1) both NO and prostaglandins are involved in the mechanism of acid inhibition in the stomach after damage with 20 mM TC, 2) the generation of NO in the stomach after injury may be a ssociated with the constitutive type of NO synthase and 3) the acid st imulatory pathway may be activated after injury, in addition to the in hibitory mechanism.