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Mechanism of Acid Secretory Changes in Rat Stomach After Damage by Taurocholate Role of Nitric Oxide, Histamine, and Sensory Neurons

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Abstract

The present study was performed to investigatethe mechanism underlying the acid stimulatory responsein the stomach after damage under the inhibition ofnitric oxide (NO) production byNG-nitro-L-arginine methyl ester (L-NAME). A rat stomach wasmounted in an ex vivo chamber, perfused with saline, andthe potential difference (PD) and acid secretion weremeasured before and after the application of 20 mM taurocholate (TC) for 30 min. Exposure of thestomach to TC caused a PD reduction and a decrease ofacid secretion. Pretreatment with L-NAME did not affectbasal acid secretion but significantly enhanced the acid secretion in the stomach after damagewith TC, without any effect on the PD response. Thiseffect of L-NAME was antagonized by simultaneousadministration of L-arginine but not D-arginine. The luminal appearance of NO was significantlyincreased in the stomach after exposure to TC, and thischange was completely blocked in the presence of L-NAMEor when EGTA was applied together with TC. The enhanced acid secretory response to TC in thepresence of L-NAME was inhibited by pretreatment withcimetidine, FPL-52694 (a mast cell stabilizer), orspantide (a substance P antagonist) or by chemical ablation of capsaicinsensitive sensory neurons.Mucosal exposure to TC increased histamine output in thelumen and decreased the number of metachromaticallystaining cells in the stomach, and these changes were also significantly prevented by FPL-52694,spantide, or sensory deafferentation. These resultssuggest that 1) damage in the stomach may activate theacid stimulatory pathway in addition to the NO-dependent inhibitory mechanism, but the latter effectovercomes the former, resulting in a decrease in acidsecretion, 2) the acid stimulation in the damagedstomach may be mediated by histamine released from the mucosal mast cell which may interact withcapsaicin-sensitive sensory nerves, and 3) L-NAMEunmasks the acid stimulatory response by suppressing theinhibitory mechanism.

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Authors
  1. Koji Takeuchi
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  2. Shinichi Kato
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  3. Tetsuya Yasuhiro
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  4. Koji Yagi
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Takeuchi, K., Kato, S., Yasuhiro, T. et al. Mechanism of Acid Secretory Changes in Rat Stomach After Damage by Taurocholate Role of Nitric Oxide, Histamine, and Sensory Neurons. Dig Dis Sci 42, 645–653 (1997). https://doi.org/10.1023/A:1018875932503

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