Luminal calcium in regulation of nitric oxide release and acid secretion in rat stomachs after damage.

ABSTRACT

We investigated the role of luminal Ca2+ in the regulation of nitric oxide (NO) release and acid secretion in the rat stomach following damage by sodium taurocholate (TC). Under urethane anesthesia, a rat stomach was mounted in an ex vivo chamber, perfused with saline, and transmucosal potential difference (PD), luminal pH, acid secretion, and luminal contents of Ca2+ and NO were measured before and after exposure to 20 mM TC for 30 min, with or without coapplication of EGTA (5 mM) and/or CaCl2 (10 mM). Mucosal exposure to TC caused a reduction in PD and a decrease of acid secretion, with a concomitant increase of NO as well as Ca2+ content in the gastric lumen. The increase of NO release as well as the reduced acid response were attenuated by pretreatment with L-NAME or coapplication of EGTA, and the latter inhibited the luminal increase of Ca2+. The changes caused by L-NAME were antagonized by coadministration of L-arginine, while those induced by EGTA were partially antagonized by coinstillation of CaCl2. Neither treatment tested had any effect on gastric PD responses to TC. These results suggest that (1) damage in the stomach increases the release of Ca2+ as well as NO in the lumen; (2) acid secretion decreases in response to damage by both an NO- and Ca2+-dependent mechanism; and (3) the increase of luminal Ca2+ is an adaptive response of the stomach to damage and may play an important role in increasing NO production and hence in regulating acid secretion.