Skip to main content
Log in

Gastrointestinal ulceration in the guinea pig in response to dimaprit, histamine, and H1-and H2-blocking agents

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

Abstract

Histamine is known to induce gastric ulcers in guinea pigs after intraperitoneal administration and duodenal ulcers after repeated intramuscular administrations. This study was undertaken to clarify further the differential role of H1 and H2 receptor sites in respect to gastric and duodenal ulcer in the guinea pig. Groups of guinea pigs were treated with histamine, intraperitoneal (1.81 mg/kg intraperitoneal) or intramuscular (0.09 mg/kg intramuscular×8 doses); the selective H2 agonist dimaprit (0.09–0.18 mg/kg×8 doses intramuscular or 1.81–3.62 mg/kg intraperitoneal); NaCl, 154 mM (control); and the selective H1 and H2 antagonists, diphenhydramine (125 mg/kg×2 doses, intramuscular) or cimetidine (50 mg/kg×3 doses, intramuscular). Gastric and duodenal lesions were evaluated and residual gastric contents were analyzed. The selective induction of gastric or duodenal ulceration by histamine was confirmed, and the H2 agonist, dimaprit, has been shown to be ulcerogenic to the guinea pig duodenum by intraperitoneal or intramuscular administration. Diphenhydramine produced considerably more protection against histamine-induced gastric ulceration (62% decrease in incidence), while cimetidine was particularly effective in the prevention of histamine-induced duodenal ulcer (64% decrease in incidence). A differential role of histamine in the pathogenesis of gastric as opposed to duodenal ulcer is suggested by the present findings.

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. Code CF, Varco RL: Chronic histamine action. Proc Soc Exp Biol 44:475–477, 1940

    Google Scholar 

  2. Schwartz JC: Gastric histamine in the pathogenesis of experimental ulcers.In Peptic Ulcer, CJ Pfeiffer (ed). Philadelphia, JB Lippincott, 1971, pp 190–198

    Google Scholar 

  3. Eagleton GB, Watt J: Acute duodenal ulceration in the guinea pig induced by repeated intramuscular injection of aqueous histamine. J Pathol Bacteriol 93:694–696, 1967

    Google Scholar 

  4. Eagleton GB, Watt J: The selective production of gastric and duodenal ulceration using histamine.In Peptic Ulcer, CJ Pfeiffer (ed). Philadelphia, JB Lippincott, 1971, pp 34–44

    Google Scholar 

  5. Black JW, Duncan WAM, Durant CJ, Ganellin CR, Parsons EM: Definition and antagonism of histamine H2-receptors. Nature 236:385–390, 1972

    Google Scholar 

  6. Safaie-Shirazi S, Foster LD, Hardy BM: The effect of metiamide, an H2-receptor antagonist, in the prevention of experimental stress ulcers. Gastroenterology 71:421–425, 1976

    Google Scholar 

  7. Belliveau P, Vas S, Himal HS: Septic induced acute gastric erosions: The role of cimetidine. J Surg Res 24:264–271, 1978

    Google Scholar 

  8. Carmichael HA, Nelson LM, Russel RI: Cimetidine and prostoglandin: Evidence for different modes of action on the rat gastric mucosa. Gastroenterology 74:1229–1232, 1978

    Google Scholar 

  9. Bianchi Porro G, Cheli R, Dobrilla G, Verme G, Molinari F, Pera A, Petrillo M, Valentini M: Treatment of active duodenal ulcer with oral cimetidine: A multicenter controlled endoscopic trait. Digestion 17:383–386, 1978

    Google Scholar 

  10. Ippoliti AF, Sturdevant RAL, Isenberg JI, Binder M, Camacho R, Cano R, Cooney C, Kline MM, Koretz RL, Meyer JH, Samloff IM, Schwabe AD, Strom EA, Valenzuela JE, Wintroub RH: Cimetidine versus intensive antacid therapy for duodenal ulcer. A multicenter trial. Gastroenterology 24:393–395, 1978

    Google Scholar 

  11. Blair EL, Grund ER, Miller IT, Reed JD, Sanders DJ, Thompson MH, Venables CW: Metiamide in the Zollinger-Ellison syndrome. Am J Dig Dis 20:1123–1130, 1975

    Google Scholar 

  12. Parsons ME, Owen DAA, Ganellin CR, Durant GJ: Dimaprit-[S-{3-(N,N-dimethylamino) propyl}isothoiurea]—a highly specific histamine H2-receptor agonist, Part 1. Pharmacology. Agents Actions 7:31–37, 1977

    Google Scholar 

  13. Carter DC, Impicciatore M, Grossman MI: Effect of dimaprit on gastric acid secretion in conscious cats. Agents Actions 8:453–457, 1978

    Google Scholar 

  14. Peterson H, Grossman MI: Stimulation of gastric acid secretion by dimaprit in unanesthetized rats. Agents Actions 8:566–567, 1978

    Google Scholar 

  15. Pfeiffer CJ, Muller PJ: Physiologic correlates dependent upon mode of death. Toxicol Appl Pharmacol 10:253–260, 1967

    Google Scholar 

  16. Sethbhadki S, Pfeiffer CJ, Roth JLA: Gastric mucosal ulceration following vasoactive agents—a new experimental model. Am J Dig Dis 15:261–270, 1970

    Google Scholar 

  17. Robert A, Standish WL: Production of duodenal ulcers, in rats, with one injection of histamine. Fed Proc 32:322, 1973

    Google Scholar 

  18. Watt T, Eagleton JB: Antihistamine projection against histamine-induced gastric ulceration in the guinea pig. J Pharm Pharmacol 16(Suppl):83T-84T, 1964

    Google Scholar 

  19. Hohnke LA: Gastric acid secretion and ulcerogenesis in histamine-treated guinea pigs. Gastroenterology 66:1161–1167, 1974

    Google Scholar 

  20. Eagleton GB, Watt J: Failure of antihistamine to protect against histamine-induced duodenal ulceration in the guinea pig. J Pharm Pharmacol 18:835–836, 1966

    Google Scholar 

  21. Dai S, Ogle CW: Effects of stress of autonomic blockers on gastric mucosal microcirculation in rats. Eur J Pharmacol 30:86–92, 1975

    Google Scholar 

  22. Cho CH, Ogle CW: Histamine H1- and H2-receptor-mediated gastric microcirculatory effects in the aetiology of stress ulceration in the rat stomach. Experientia 34:1294–1295, 1978

    Google Scholar 

  23. Guth PH, Smith E: Histamine receptors in the gastric microcirculation. Gut 19:1059–1063, 1978

    Google Scholar 

  24. Cho CH, Ogle CW: Cholinergic mediated gastric mass cell degranulation with subsequent histamine H1- and H2-receptor activation in stress ulceration. Eur J Pharmacol 55:23–33, 1979

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cho, C.H., Pfeiffer, C.J. Gastrointestinal ulceration in the guinea pig in response to dimaprit, histamine, and H1-and H2-blocking agents. Digest Dis Sci 26, 306–311 (1981). https://doi.org/10.1007/BF01308370

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01308370

Keywords

Navigation