Nitric oxide and prostaglandins in regulation of acid secretory response in rat stomach following injury.
The gastric mucosa responds to taurocholate (TC) by significantly decreasing acid secretion. We examined the role of nitric oxide (NO) in this phenomenon in comparison with endogenous prostaglandins. A rat stomach was mounted in an ex-vivo chamber and perfused with saline, and the potential difference, luminal pH and acid responses were measured before and after the application of 20 mM TC for 30 min with or without pretreatment with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or the cyclooxygenase inhibitor indomethacin. Exposure of the stomach to TC caused a reduction in potential difference, a decrease in acid secretion and an increase in luminal HCO3-. Pretreatment 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 that of indomethacin, and, especially in the presence of L-NAME, acid secretion was actually enhanced after exposure to TC. Aminoguanidine, the selective inhibitor of inducible NO synthase, did not have any significant effect on either parameter. This effect of L-NAME was antagonized by the simultaneous administration of L-arginine but not by that of D-arginine, whereas the effect of indomethacin was reversed by PGE2. Acid secretion in normal stomachs was significantly reduced by nitroprusside and PGE2 but was not affected by either L-NAME or indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Yamashina, Japan.
Takehara
K
K
Kaneko
T
T
Okabe
S
S
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012636:Secretory Rate / Q000187:drug effects; D013656:Taurocholic Acid / Q000494:pharmacology*
D001639:Bicarbonates; D006146:Guanidines; D011453:Prostaglandins; D009599:Nitroprusside; D009569:Nitric Oxide; D000431:Ethanol; D013656:Taurocholic Acid; D006632:Histamine; D001120:Arginine; D015232:Dinoprostone; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin