Vol. 301, Issue 3, 969-974, June 2002

Role of ATP-Sensitive Potassium Channels in Prostaglandin-Mediated Gastroprotection in the Rat

Brigitta M. Peskar, Karlheinz Ehrlich and Bernhard A. Peskar

Department of Experimental Clinical Medicine, Ruhr University of Bochum, Bochum, Germany (B.M.P., K.E.); and Department of Experimental and Clinical Pharmacology, University of Graz, Graz, Austria (B.A.P.)

This study compares the involvement of ATP-sensitive potassium (K_ATP) 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 K_ATP 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 K_ATP channel activator cromakalim (0.3-0.5 mg/kg). In conclusion, our results indicate a role of K_ATP 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 K_ATP channels, and this mechanism, at least in part, mediates gastroprotection.