Skip to main content
Log in

Involvement of α2-Adrenoceptors in mechanism of intragastric nicotine protection against ethanol injury in rat stomach

  • Original Articles
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

To elucidate the role of α- and β-adrenoceptors in the mechanism of intragastric nicotine protection against ethanol-induced gastric mucosal injury, the following studies were performed. At 0.5-hr prior to the injury study, rats were pretreated with: subcutaneous control, prazosin (0.5 mg/kg) or yohimbine (5 mg/kg) to block α1- or α2-adrenoceptors; or intraperitoneal control, metoprolol (2 mg/kg) or butoxamine (4 mg/kg) to block β1- or β2-adrenoceptors, respectively. At 1-hr intervals, rats received intragastric vehicle or nicotine (4 mg/kg) and 40% ethanol (10 ml/kg). Total lengths of the linear gastric corpus mucosal lesions were measured by an unbiased observer using a caliper. In a separate study, 0.5-hr after subcutaneous control or yohimbine (5 mg/kg), rats were treated with intragastric vehicle or nicotine (4 mg/kg). One hour later, gastric mucus volume, gastric juice volume and pH, and titratable acid in the gastric juice were measured. In the rat stomach, the intragastric nicotine protection against 40% ethanol-induced mucosal injury was not blocked by selective α1-(prazosin), β1-(metoprolol), or β2-(butoxamine) adrenoceptor antagonists. The protection was significantly reduced although not completely abolished by selective α2-(yohimbine) adrenoceptor antagonist. Yohimbine also significantly reduced basal and nicotine-stimulated increase in gastric mucus volume. These data suggest that α2-adrenoceptors are involved in the protective effect of intragastric nicotine against 40% ethanol-induced gastric mucosal injury possibly by a mucus-dependent mechanism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Endoh K, Baker M, Leung FW: Mechanism of intragastric nicotine protection against ethanol-induced gastric injury. Dig Dis Sci 36:39–46, 1991

    Google Scholar 

  2. 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

    Google Scholar 

  3. Costa M, Gabella G: Adrenergic innervation of the alimentary canal. Z Zellforsch 122:357–377, 1971

    Google Scholar 

  4. Ben-Zvi Z, Leibson V: Antiulcer activity of clonidine: lack of effect on gastric prostaglandins. Prostaglandins Leukotrienes Med 30:51–59, 1987

    Google Scholar 

  5. Gaetani M, Debeus R: Action ofl-dopa, norepinephrine and amantadine on ulcers caused by reserpine in the rat. Digestion 7:302–311, 1972

    Google Scholar 

  6. Kunchandy J, Khanna S, Kulkarni SK: Effect of alpha2 agonists clonidine, guanfacine and B-HT 920 on gastric acid secretion and ulcers in rats. Arch Int Pharmacodyn Ther 275:123–138, 1985

    Google Scholar 

  7. Nakane S, Sakai T: Effects of biogenic monoamines and precursors on stress ulcers and secretion in stomach. Jpn J Pharmacol 24:241–246, 1974

    Google Scholar 

  8. Orlando RC, Hernandez DE, Prange AJ Jr, Nemeroff CB: Role of the autonomic nervous system in the cytoprotective effect of neurotensin against gastric stress ulcers in rats. Psychoneuroendocrinology 10:149–157, 1985

    Google Scholar 

  9. Esplugues J, Lloris JM, Martí-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

    Google Scholar 

  10. 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

    Google Scholar 

  11. 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

    Google Scholar 

  12. Ritchie WP Jr, Shearburn EW III: Influence of isoproterenol and cholestyramine on acute gastric mucosal ulcerogenesis. Gastroenterology 73:62–65, 1977

    Google Scholar 

  13. 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

    Google Scholar 

  14. Nylander O, Flemström G: Effects of alpha-adrenoceptor agonists and antagonists on duodenal surface epithelial HCO3 secretion in the ratin vivo. Acta Physiol Scand 126:433–441, 1986

    Google Scholar 

  15. DiJoseph JF, Taylor JA, Mir GN: Alpha-2 receptors in the gastrointestinal system—a new therapeutic approach. Life Sci 35:1031–1042, 1984

    Google Scholar 

  16. Cambridge D, Davey MJ, Massingham R: Prazosin, a selective antagonist of post-synaptic α-adrenoceptors. Br J Pharmacol 59:514P-515P, 1977

    Google Scholar 

  17. Hoffman BB, Lefkowitz RJ: Catecholamines and sympathomimetic drugs.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 187–220

    Google Scholar 

  18. Green GJ, Wilson H, Yates MS: The mechanism of the clonidine-induced reduction in peripheral parasympathetic submaxillary salivation. Eur J Pharmacol 56:331–336, 1979

    Google Scholar 

  19. Goldberg MR, Robertson D: Yohimbine: a pharmacological probe for study of the α2-adrenoreceptor. Pharmacol Rev 35:143–180, 1983

    Google Scholar 

  20. Ruppin H, Person B, Robert A, Domschke W: Gastric cytoprotection in man by prostaglandin E2. Scand J Gastroenterol 16:647–652, 1981

    Google Scholar 

  21. Agrawal NM, Godiwala T, Arimura A, Dajani EZ: Cytoprotection by a synthetic prostaglandin against ethanol-induced gastric mucosal damage—a double-blind endoscopic study in human subjects. Gastrointest Endosc 32:67–70, 1986

    Google Scholar 

  22. 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

    Google Scholar 

  23. Brogden RN, Heel RC, Speight TM, Avery GS: Metoprolol: A review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris. Drugs 14:321–348, 1977

    Google Scholar 

  24. Levy B: The adrenergic blocking activity ofN-tert-butylmethoxamine (butoxamine). J Pharmacol Exp Ther 151:413–422, 1966

    Google Scholar 

  25. Paul V: Involvement of β2-adrenoceptor blockade and 5-hydroxytryptamine mechanism in inhibition of harmaline-induced tremors in rats. Eur J Pharmacol 122:111–115, 1986

    Google Scholar 

  26. Endoh K, Ro G, Leung FW: Intragastric nicotine protects against 40% ethanol-induced gastric mucosal injury despite pretreatment with propranolol orN-ethylmaleimide in rats. Dig Dis Sci 37:391–396, 1992

    Google Scholar 

  27. Allen A, Carroll NJH: Adherent and soluble mucus in the stomach and duodenum. Dig Dis Sci 30(suppl):55S-62S, 1985

    Google Scholar 

  28. Grisham MB, Ritter CV, Smith BF, Lamont JT, Granger DN: Interaction between oxygen radicals and gastric mucin. Am J Physiol 253:G93-G96, 1987

    Google Scholar 

  29. Phipps RJ, Nadel JA, Davis B: Effect of alpha-adrenergic stimulation on mucus secretion and on iron transport in cat tracheain vitro. Am Rev Respir Dis 121:359–365, 1980

    Google Scholar 

  30. 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

    Google Scholar 

  31. Cullum VA, Farmer JB, Jack D, Levy GP: Salbutamol—a new, selective β-adrenoceptive receptor stimulant. Br J Pharmacol 35:141–151, 1969

    Google Scholar 

  32. 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

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by Veternas Administration Medical Research Funds, and in part by research grants (0162-01, 02, and 291-01) 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 F.W.L. Dr. Endoh is a recipient of the University of California Tobacco-Related Disease Research Program Research Fellowship Award (FT 37).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Endoh, K., Kao, J., Baker, M. et al. Involvement of α2-Adrenoceptors in mechanism of intragastric nicotine protection against ethanol injury in rat stomach. Digest Dis Sci 38, 713–721 (1993). https://doi.org/10.1007/BF01316805

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01316805

Key Words

Navigation