title: Interactive roles of endogenous prostaglandin and nitric oxide in regulation of acid secretion by damaged rat stomachs.
abstract: BACKGROUND
  The acid inhibitory mechanism in the damaged stomach is known to involve endogenous nitric oxide (NO) as well as prostaglandin (PG).
  
  
  OBJECTIVE
  To investigate the interaction between PG and NO in regulation of acid secretion in the stomach following damage.
  
  
  METHODS
  Under urethane anaesthesia, a rat stomach was mounted in an ex vivo chamber and perfused with saline. Acid secretion, luminal PGE2, NO metabolites (NOx) and histamine output were measured before and after application of 20 mM taurocholate Na (TC) for 30 min, with or without pre-treatment with indomethacin and/or N(G)-nitro-L-arginine methyl ester (L-NAME).
  
  
  RESULTS
  Exposure of the stomach to TC caused a decrease in acid secretion, with concomitant increase of both luminal NOx and PGE2. Either L-NAME or indomethacin reduced the decrease in acid secretion in response to TC, but only L-NAME allowed acid secretion to increase over basal values. L-NAME prevented the increase of luminal NOx after TC treatment, while indomethacin inhibited PGE2 release during and after exposure to TC. The increase in acid secretion in the presence of L-NAME was prevented when indomethacin was given concomitantly. TC treatment increased histamine output in the lumen, a process that was enhanced by L-NAME but reduced by indomethacin.
  
  
  CONCLUSIONS
  Damage to the stomach increases both NO and PG in the lumen, and decreases acid secretion. Inhibiting NO production increases acid secretion in the damaged stomach, but only when PG biosynthesis is intact. It is assumed that endogenous PG has a dual role in the regulation of acid secretion in the damaged stomach: an inhibitory effect at the parietal cell and an excitatory effect probably through enhancing the release of mucosal histamine.
authors.affiliation: Department of Pharmacology & Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Japan. takeuchi@mb.kyoto-phu.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
authors.forename: S
authors.initials: S
authors.lastname: Sugamoto
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Kawauchi
authors.forename: K
authors.initials: K
authors.lastname: Tashima
mesh_terms: D000818:Animals; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D006636:Histamine Release; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009924:Organ Culture Techniques; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000494:pharmacology
chemical_list: D002756:Cholagogues and Choleretics; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D009569:Nitric Oxide; D013656:Taurocholic Acid; D019331:NG-Nitroarginine Methyl Ester