Abstract
We tested the hypotheses that the protective effect of intragastric nicotine against ethanol-induced gastric mucosal injury is dependent on propranolol- orN-ethylmaleimide-sensitive mechanisms. Propranolol was administered in doses (2 and 20 mg/kg) that provided dose-related blockade of β-adrenoceptors (significant decreases in heart rate).N-Ethylmaleimide was administered in doses that previously had been shown to increase gastric vascular permeability (10 mg/kg) or inhibit gastric mucosal sulfhydryl compounds (50 mg/kg). At 0.5 hr after these or control subcutaneous pretreatments, the rats received intragastric nicotine (4 mg/kg) or vehicle. One hour later 40% ethanol was given intragastrically. The gastric corpus mucosal lesions were recorded by polaroid photographs after another hour, and their areas measured unbiasedly by computerized image analysis. The results showed thatN-ethylmaleimide, but not propranolol, aggravated ethanol-induced gastric mucosal injury. The protective effect of intragastric nicotine was not modified by either pretreatment. We conclude that the mechanism mediating intragastric nicotine protection against 40% ethanol-induced gastric mucosal injury is independent of propranolol- orN-ethylmaleimide-sensitive mechanisms.
Similar content being viewed by others
References
Wong SH, Ogle CW, Cho CH: The influence of chronic or acute nicotine pretreatment on ethanol-induced gastric ulceration in the rat. J Pharm Pharmacol 38:537–540, 1986
Endoh K, Baker M, Leung FW: Mechanism of intragastric nicotine protection against ethanol-induced gastric injury. Dig Dis Sci 36:39–46, 1991
Kékes-Szabó A: Pharmacological control of experimental ulcers with special regard to sympathetic activation.In Progress in Peptic Ulcer, GY Mózsik, T Jávor (eds). Budapest, Akadémiai Kiadó, 1976, pp 433–483
Fielding LP, Raute M, Curwain BP: Effect of salbutamol on acute gastric ulceration induced by indomethacin in the rat. Eur Surg Res 9:252–257, 1977
Ritchie WP Jr, Shearburn EW III: Influence of isoproterenol and cholestyramine on acute gastric mucosal ulcerogenesis. Gastroenterology 73:62–65, 1977
Moody FG, McGreevy J, Zalewsky C, Cheung LY, Simons M: The cytoprotective effect of mucosal blood flow in experimental erosive gastritis. Acta Physiol Scand (special suppl):35–43, 1978
Esplugues J, Lloris JM, Marté-Bonmatí E, Morcillo EJ: Effects of β-adrenoceptor drug stimulation on various models of gastric ulcer in rats. Br J Pharmacol 76:587–594, 1982
Howard TJ, Passaro E Jr, Guth PH: Topical isoproterenol protects the rat gastric mucosa from ethanol-induced injury. J Surg Res 46:640–645, 1989
Szabo S, Trier JS, Frankel PW: Sulfhydryl compounds may mediate gastric cytoprotection. Science 214:200–202, 1981
Bálint GA, Varró V: On the cytoprotective action of sulfhydryl-containing substances. Acta Physiol Acad Sci Hung 60:139–142, 1982
Johansson C, Bergström S: Prostaglandins and protection of the gastroduodenal mucosa. Scand J Gastroenterol 17(suppl 77):21–46, 1982
Strubelt O, Hoppenkamps R: Relations between gastric glutathione and the ulcerogenic action of non-steroidal anti-inflammatory drugs. Arch Int Pharmacodyn Ther 262:268–278, 1983
Konturek SJ, Brozozowski T, Piastucki I, Radecki T, Dupuy D, Szabo S: Gastric mucosal protection by agents altering gastric mucosal sulfhydryls—role of endogenous prostaglandins. Digestion 37:65–71, 1987
Rogers C, Brown A, Szabo S: Gastric mucosal protection by new aryl sulfhydryl drugs. Dig Dis Sci 33:324–329, 1988
Hirota M, Inoue M, Ando Y, Hirayama K, Morino Y, Sakamoto K, Mori K, Akagi M: Inhibition of stress-induced gastric injury in the rat by glutathione. Gastroenterology 97:853–859, 1989
Robert A, Nezamis JE, Lancaster C, Hanchar AJ: Cytoprotection by prostaglandins in rats—prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury. Gastroenterology 77:433–443, 1979
Hoffman BB, Lefkowitz RJ: Adrenergic receptor antagonists.In Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, AG Gilman, TW Rall, AS Nies, P Taylor (eds). New York, Pergamon Press, 1990, pp 221–243
Lo SK, Leung FW, Guth PH: Protection against absolute-ethanol-induced gastric antral and corpus mucosal injury—a gross and histologic study. Dig Dis Sci 33:1403–1408, 1988
Webb JL:N-Ethylmaleimide.In Enzyme and Metabolic Inhibitors, Vol III, JL Webb (ed). New York, Academic Press, 1966, pp 337–365
Takeuchi K, Okada M, Niida H, Okabe S: Role of sulfhydryls in mucosal injury caused by ethanol—relation to microvascular permeability, gastric motility and cytoprotection. J Pharmacol Exp Ther 248:836–841, 1989
Costa M, Gabella G: Adrenergic innervation of the alimentary canal. Z Zellforsch 122:357–377, 1971
Ekue JMK, Shanks RG, Zaidi SA: Comparison of the effects of isoprenaline, orciprenaline, salbutamol and isoetharine on the cardiovascular system of anesthetized dogs. Br J Pharmacol 43:23–31, 1971
Cullum VA, Farmer JB, Jack D, Levy GP: Salbutamol—a new, selective β-adrenoceptive receptor stimulant. Br J Pharmacol 35:141–151, 1969
Hoppenkamps R, Thies E, Younes M, Siegers C-P: Glutathione and GSH-dependent enzymes in the human gastric mucosa. Klin Wochenschr 62:183–186, 1984
Boyd SC, Sasame HA, Boyd MR: High concentrations of glutathione in glandular stomach—possible implications for carcinogenesis. Science 205:1010–1012, 1979
Szabo S: Experimental basis for a role for sulfhydryls and dopamine in ulcerogenesis—a primer for cytoprotection-organoprotection. Klin Wochenschr 64(suppl VII):116–122, 1986
Miller TA, Li D, Kuo Y-J, Schmidt KL, Shanbour LL: Nonprotein sulfhydryl compounds in canine gastric mucosa—effects of PGE2 and ethanol. Am J Physiol 249(Gastrointest Liver Physiol 12):G137-G144, 1985
Author information
Authors and Affiliations
Additional information
Supported by Veterans Administration Medical Research Funds, and in part by research grants (0162-01, 02 and 0291-01) from the Smokeless Tobacco Research Council, Inc., and by funds (1RT 80) provided by the Cigarette and Tobacco Surtax Fund of the State of California through the Tobacco-Related Disease Research Program of the University of California to FWL. Dr. Endoh is a recipient of the University of California Tobacco-Related Disease Research Program Research Fellowship Award (FT 37).
Rights and permissions
About this article
Cite this article
Endoh, K., Ro, G. & Leung, F.W. Intragastric nicotine protects against 40% ethanol-induced gastric mucosal injury despite pretreatment with propranolol orN-ethylmaleimide in rats. Digest Dis Sci 37, 391–396 (1992). https://doi.org/10.1007/BF01307733
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01307733