Stimulation of duodenal bicarbonate secretion by misoprostol.
Graded doses of topical misoprostol were examined for effects on duodenal bicarbonate output in fasted conscious rats and compared with perfusions of the H2-receptor blocker cimetidine. Chronic loops (2 cm) of the proximal duodenum were prepared in male Sprague-Dawley rats weighing 250 g. A thin perfusion tube was placed in the duodenal bulb, and a permanent cannula drained the distal end to the exterior. The stomach and remaining duodenum with biliary and pancreatic ducts were then reanastomosed. During tests, the loops were perfused with isotonic saline at 0.5 ml/min and samples of 15-min effluents analyzed for HCO3- using a modified back-titration method. Drugs and stimulants were added to the perfusion fluid. Misoprostol at 10(-10) M significantly (P less than 0.02) elevated the duodenal HCO3- from basal value (N = 10), and concentrations of 10(-10) to 4 X 10(-4) M produced dose-dependent increases of bicarbonate secretion, with a peak output of 49 +/- 7 mumol/cm/hr. A peak response of the same magnitude, 42 +/- 4 mumol/cm/hr, is observed after 5-min exposure of the loops to 150 mm HCl. The response to a single dose of 10(-4) M misoprostol was sustained, similar to the prolonged stimulatory effects of 5-min acid exposure. Perfusions of the loop with graded natural PGE2 result in similar increases of duodenal HCO3-, but the peak may be lower and the response to a single dose is less sustained. The H2-receptor blocker cimetidine, perfused at concentrations of 10(-7) to 10(-4) M failed to affect duodenal HCO3- output.(ABSTRACT TRUNCATED AT 250 WORDS)
Smedfors
B
B
Johansson
C
C
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism*; D002927:Cimetidine / Q000494:pharmacology; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016595:Misoprostol; D010477:Perfusion; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000897:Anti-Ulcer Agents; D001639:Bicarbonates; D011458:Prostaglandins E; D016595:Misoprostol; D002927:Cimetidine; D000527:Alprostadil; D015232:Dinoprostone