Abstract
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.
Footnotes
- Abbreviations:
- PG
- prostaglandin
- CGRP
- calcitonin gene-related peptide
- KATP channels
- ATP-sensitive potassium channels
- Received November 26, 2001.
- Accepted March 4, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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