Gastric HCO3- secretion induced by mucosal acidification: different mechanisms depending on acid concentration.
We compared the HCO3- secretory responses induced by mucosal acidification at different HCl concentrations (100 and 200 mM HCl) in the rat stomach. Under urethane anesthesia, the stomach was mounted on an ex vivo chamber and perfused with saline under inhibition of acid secretion by omeprazole (60 mg/kg, i.p.). TheHCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. The acidification was performed by exposure of the mucosa to 100 mMor 200 mM HCl for 10 min. The secretion of HCO3- was increased by acidification of the mucosa at both 100 and 200 mM of HCl, and the maximal HCO3- response was 1.5-times greater at the latter concentration. The HCO3- responses induced by 100 and 200 mM HCl were both totally inhibited by prior administration of indomethacin, an inhibitor of prostaglandin (PG) production. The HCO3- stimulatory effect of 200 mM HCl was also significantly attenuated by pre-treatment with N(G)-nitro L-arginine methyl ester (L-NAME), the inhibitor of nitric oxide (NO) synthase, as well as chemical ablation of capsaicin-sensitive afferent neurons, whereas that of 100 mM HCl was affected by neither of these treatments. We conclude that the mucosal acidification stimulates gastric HCO3- secretion in different mechanisms, depending on the concentration of acid; the response caused by 100 mM HCl is mediated only by PGs, while that caused by 200 mM HCl is mediated by both capsaicin-sensitive afferent neurons and NO, in addition to PGs.
Aihara
Eitaro
E
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Hayashi
Masamune
M
Sasaki
Yoko
Y
Takeuchi
Koji
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism*; D006851:Hydrochloric Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001639:Bicarbonates; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D006851:Hydrochloric Acid; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin