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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.

Multiple calcium sources are required for intracellular calcium mobilization during gastric organoid epithelial repair

“…Some of such mechanisms have been shown to cause Ca 2+ mobilization that is highly localized, brief increases in Ca 2+ while other pathway mechanisms produce longer-lasting elevations of Ca 2+ , which often follow oscillations caused by feedback loops within the signaling system (Berridge, 1997). In vivo gastric damage elicits increased gastric luminal Ca 2+ (Koo, 1994;Takeuchi, Kato, Konaka, & Sugawa, 1999;Takeuchi et al, 1985). While intracellular Ca 2+ appears to be localized within the cells adjacent to the damaged site, previous studies have been limited in investigating Ca 2+ mobilization within an in vitro model that closely mirrors in vivo native, noncancerous tissue.…”

Importance of Ca2+ in gastric epithelial restitution—new views revealed by real-time in vivo measurements

“…In contrast, evidence from cultured cells suggests that neither cAMP nor cGMP plays any role in gastric epithelial cell migration [21,63]. Conversely, luminal Ca 2+ likely stimulates cNOS-dependent nitric oxide/cGMP production resulting in facilitating gastric restitution due to inhibition of acid secretion or increase of bicarbonate secretion [24,64]. This set of results leaves space for Ca 2+ and its signaling to take a central role in gastric epithelial cell restitution.…”

“…In such models, restitution required >4 hr to complete [2,22,23]. When gastric restitution was measured in ex vivo chambered stomach in anesthetized animals by detecting transmucosal potential difference, repair of damage was completed in 1-2 hr [24,25]. The different time courses may be related to different modes of inducing damage, or variable potency of tissue preparations to mount a robust damage response.…”

“…Critchlow et al first demonstrated almost 30 years ago that an adequate extracellular Ca 2+ level (changed conditions on the serosal side of isolated tissues in Ussing chamber) is required for complete restitution of isolated frog gastric mucosa after hyperosmolar injury, and that restitution occurs by migration of persisting viable gastric pit cells [2]. Similarly, in response to pervasive surface gastric damage caused by taurocholate, or 30% ethanol, the gastric luminal Ca 2+ increased in the collected gastric effluent [24,46]. In the focal damage model after photodamage, we recently reported that luminal Ca 2+ increased (Figure 1B) [12].…”