Possible role of endogenous prostaglandins in alkaline response in rat gastric mucosa damaged by hypertonic NaCl.
Changes in gastric potential difference (PD) and luminal pH of gastric perfusate were studied in anesthetized rats before and after application of hypertonic NaCl to the stomach for 10 min. There was a concentration-dependent reduction of PD and an increase in luminal pH after exposure to NaCl. In the stomach exposed to NaCl over 0.75 M, a significant amount of HCO3- (0.5-1.5 mumol/10 min) was titrated in the lumen at pH 7.4 under cimetidine infusion (8 mg/kg/hr). After removal of hypertonic NaCl, the PD returned completely or partially to the basal values within 1 hr. Pretreatment of the rats with subcutaneously administered indomethacin (3 mg/kg) or aspirin (100 mg/kg) significantly inhibited the recovery of PD in the 1 M NaCl-treated stomach. Gastric alkaline response in the damaged mucosa was significantly attenuated in rats pretreated with indomethacin or aspirin. Intravenously administered cimetidine (8 mg/kg/hr) or subcutaneously administered 16,16-dimethyl prostaglandin E2 (3 micrograms/kg) abolished the inhibitory effect of indomethacin on gastric alkaline response caused by 1 M NaCl, and partially restored the PD recovery. These results indicate that endogenous prostaglandins released in the injured mucosa are probably responsible for the luminal alkalinization noted after exposure to 1 M NaCl. This process would lead to a protection against further damage and accelerate reestablishment of the mucosal integrity.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D006982:Hypertonic Solutions; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology*
D006982:Hypertonic Solutions; D011453:Prostaglandins; D011458:Prostaglandins E; D012965:Sodium Chloride; D002927:Cimetidine; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin