RT Journal Article
SR Electronic
T1 Role of ATP-Sensitive Potassium Channels in Prostaglandin-Mediated Gastroprotection in the Rat
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 969
OP 974
DO 10.1124/jpet.301.3.969
VO 301
IS 3
A1 Peskar, Brigitta M.
A1 Ehrlich, Karlheinz
A1 Peskar, Bernhard A.
YR 2002
UL http://jpet.aspetjournals.org/content/301/3/969.abstract
AB This study compares the involvement of ATP-sensitive potassium (KATP) channels and prostaglandins in various forms of gastroprotection in the rat. Instillation of 1 ml of 70% ethanol induced severe gastric mucosal damage (lesion index 39 ± 0.8), which was substantially but not maximally reduced by oral pretreatment with 16,16-dimethyl-prostaglandin (PG) E2 (75 ng/kg), 20% ethanol (1 ml), sodium salicylate (15 mg/kg), the metal salt lithium chloride (7 mg/kg), the sulfhydryl-blocking agent diethylmaleate (5 mg/kg), and the thiol dimercaprol (10 mg/kg). Administration of indomethacin (20 mg/kg) increased gastric mucosal damage induced by 70% ethanol (lesion index 45 ± 0.8) and significantly reduced the protective effect of 20% ethanol, sodium salicylate, lithium chloride, diethylmaleate, and dimercaprol. The blocker of KATP channels glibenclamide (5–10 mg/kg) significantly antagonized the protective effect of 16,16-dimethyl-PGE2, 20% ethanol, sodium salicylate, lithium chloride, diethylmaleate, and dimercaprol. The inhibition of protection induced by glibenclamide was reversed by pretreatment with the KATP channel activator cromakalim (0.3–0.5 mg/kg). In conclusion, our results indicate a role of KATP channels in the gastroprotective effect of 16,16-dimethyl-PGE2 and of the other agents tested. Since the protection afforded by these agents is additionally indomethacin-sensitive, it is suggested that under these conditions endogenous prostaglandins act as activators of KATPchannels, and this mechanism, at least in part, mediates gastroprotection. The American Society for Pharmacology and Experimental Therapeutics