Diazoxide, a K(ATP) opener, accelerates restitution of ethanol or indomethacin-induced gastric ulceration in rats independent of polyamines.
OBJECTIVE
Experimental acute gastric ulcerations (EAGU) are healed very rapidly. This healing process has two steps; mucosal restitution and delayed repair. Adenosine 5'-triphosphate (ATP)-dependent potassium channels (K(ATP)) have a regulatory role in the gastrointestinal physiology. In the present study, the effects of K(ATP) channel modulators; diazoxide (channel opener) and glibenclamide (channel antagonist) on the healing of EAGU were investigated. The effect of polyamine (mediators presumably responsible for restitution) biosynthesis by difluoromethylornithine (DFMO) on diazoxide-induced alterations, and the effects of acid secretion inhibitors (cimetidine, omeprazole and atropine) on the mucosal restitution of EAGU were also studied.


METHODS
Groups of 10 male rats were starved for 24 h and EAGU was induced by oral administration of 1 mL 60% ethanol or a subcutaneous injection of 30 mg/kg indomethacin. Different groups were subjected to various doses of diazoxide (5, 15, 45 mg/kg) and/or glibenclamide (2, 6, 18 mg/kg) administered intraperitoneally (i.p.) after EAGU induction. Polyamine biosynthesis was inhibited by a single i.p. injection of DFMO (500 mg/kg), administered 10 min before EAGU induction. Cimetidine, omeprazole or atropine were administered intraperitoneally at doses of 200, 5 and 1 mg/kg, respectively, after EAGU induction. Animals were killed and their gastric mucosa was examined for ulcerations.


RESULTS
Diazoxide accelerated the healing of EAGU, whereas glibenclamide aggravated EAGU. The concomitant administration of glibenclamide antagonized the diaoxide effect. Diazoxide-induced acceleration of mucosal restitution was not abolished by DFMO. Cimetidine, omeprazole and atropine had no effect on the healing of EAGU.


CONCLUSIONS
The K(ATP) channels may play an important role in the gastric mucosal restitution independent of polyamines. Acid inhibition cannot reverse EAGU.
Rahgozar
M
M
Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Iran.
Pazokitoroudi
H
H
Bakhtiarian
A
A
Djahanguiri
B
B
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003981:Diazoxide / Q000494:pharmacology*; D000431:Ethanol; D005905:Glyburide / Q000494:pharmacology; D007213:Indomethacin; D008297:Male; D011073:Polyamines / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000503:physiopathology*; D014945:Wound Healing / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011073:Polyamines; D015221:Potassium Channels; D000431:Ethanol; D003981:Diazoxide; D005905:Glyburide; D007213:Indomethacin