Stimulation of acid secretion in rat stomach following exposure to taurocholate in the presence of the nitric oxide synthase inhibitor.
1. The role of nitric oxide (NO) in the acid secretory response of the rat stomach following damage was investigated. A rat stomach was mounted in an ex-vivo chamber, perfused with saline, and the potential difference (PD), luminal pH, acid and HCO3- responses were measured before and after the mucosal exposure to 20 mM taurocholate (TC) for 30 min, with or without pretreatment with NG-nitro-L-arginine methyl ester (L-NAME). 2. Exposure of the stomach to TC caused a reduction of PD, a decrease of acid secretion and an increase in luminal HCO-. Pretreatment with L-NAME did not affect such PD and HCO3- responses, but completely attenuated the decreased acid secretory response and rather enhanced this secretion. 3. These effects of L-NAME were significantly antagonized by the co-administration of L-arginine but not D-arginine. The enhanced acid secretory response in the presence of L-NAME was significantly inhibited by prior administration of cimetidine or FPL-52694 (a mast-cell stabilizer). 4. The mucosal exposure to TC significantly decreased the number of mucosal mast cells and increased the luminal histamine output. 5. Damage in the stomach may activate the histamine-dependent acid stimulatory pathway in addition to the NO-dependent inhibitory mechanism, although the latter effect overcomes the former, resulting in a decrease of acid secretion. L-NAME unmasks the stimulation of acid secretion by suppressing the inhibitory pathway.
Takeuchi
K
K
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan.
Yasuhiro
T
T
Asada
Y
Y
Kato
S
S
Ishihara
Y
Y
D000818:Animals; D002452:Cell Count; D002867:Chromones / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000494:pharmacology*
D002867:Chromones; D004791:Enzyme Inhibitors; D005765:Gastrointestinal Agents; D006635:Histamine H2 Antagonists; C029061:FPL-52694; D013656:Taurocholic Acid; D002927:Cimetidine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester