Role of Gastric Mucosal Blood Flow in Gastroprotective Effect of Novel Xanthine Derivative

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 1994 Mar 1

PMID 8131697

Authors

T Tanaka

P H Guth

Affiliations

Soon will be listed here.

Abstract

The effect of 3-ethyl-1-(6-hydroxy-6-methylheptyl)-7-propylxanthine (A90 6119) on 40% ethanol-induced gastric lesions and gastric mucosal blood flow was investigated in rats. Gastric mucosal blood flow was measured by the hydrogen gas clearance technique and the test compounds and vehicle were administered intraduodenally. A90 6119 dose-dependently increased gastric mucosal blood flow and decreased gross and histologic gastric mucosal injury induced by 40% ethanol. Both the gastric mucosal blood flow and protective effects of A90 6119 were completely attenuated by pretreatment with indomethacin. The findings demonstrate that A90 6119 protects against ethanol-induced gastric injury, and this effect involves stimulation of endogenous prostaglandin synthesis and an increase in gastric mucosal blood flow.

References

Ito S, Lacy E . Morphology of rat gastric mucosal damage, defense, and restitution in the presence of luminal ethanol. Gastroenterology. 1985; 88(1 Pt 2):250-60. DOI: 10.1016/s0016-5085(85)80178-5. View

Pique J, Leung F, Tan H, Livingston E, Scremin O, Guth P . Gastric mucosal blood flow response to stimulation and inhibition of gastric acid secretion. Gastroenterology. 1988; 95(3):642-50. DOI: 10.1016/s0016-5085(88)80010-6. View

Holzer P, Livingston E, Guth P . Sensory neurons signal for an increase in rat gastric mucosal blood flow in the face of pending acid injury. Gastroenterology. 1991; 101(2):416-23. DOI: 10.1016/0016-5085(91)90020-l. View

Livingston E, REEDY T, Leung F, Guth P . Computerized curve fitting in the analysis of hydrogen gas clearance curves. Am J Physiol. 1989; 257(4 Pt 1):G668-75. DOI: 10.1152/ajpgi.1989.257.4.G668. View

Tanaka T, Bickel M, Herling A, Sakurai M, Goto M, Hayashi S . Effects of the novel anti-ulcer agent 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine on experimental ulcers and gastric secretion in rats. Arzneimittelforschung. 1989; 39(6):689-94. View

Guth P . Gastric blood flow in ethanol injury and prostaglandin cytoprotection. Scand J Gastroenterol Suppl. 1986; 125:86-91. DOI: 10.3109/00365528609093822. View

Saperas E, KAUFFMAN G, Tache Y . Role of central prostaglandin E2 in the regulation of gastric acid secretion in the rat. Eur J Pharmacol. 1991; 209(1-2):1-7. DOI: 10.1016/0014-2999(91)90002-8. View

Cheung L . Topical effects of 16,16-dimethyl prostaglandin E2 on gastric blood flow in dogs. Am J Physiol. 1980; 238(6):G514-9. DOI: 10.1152/ajpgi.1980.238.6.G514. View

Konturek S, RADECKI T, Brzozowski T, Piastucki I, Dembinska-Kiec A, Zmuda A . Gastric cytoprotection by prostaglandins, ranitidine, and probanthine in rats. Role of endogenous prostaglandins. Scand J Gastroenterol. 1981; 16(1):7-12. View

10.

Howard T, PASSARO Jr E, Guth P . Topical isoproterenol protects the rat gastric mucosa from ethanol-induced injury. J Surg Res. 1989; 46(6):640-5. DOI: 10.1016/0022-4804(89)90036-x. View

11.

Debas H, COHEN M, HOLUBITSKY I, Harrison R . Caffeine-stimulated acid and pepsin secretion: dose-response studies. Scand J Gastroenterol. 1971; 6(5):453-7. DOI: 10.3109/00365527109180725. View

12.

Whittle B . Mechanisms underlying gastric mucosal damage induced by indomethacin and bile-salts, and the actions of prostaglandins. Br J Pharmacol. 1977; 60(3):455-60. PMC: 1667280. DOI: 10.1111/j.1476-5381.1977.tb07522.x. View

13.

Robert A, NEZAMIS J, Lancaster C, Davis J, Field S, Hanchar A . Mild irritants prevent gastric necrosis through "adaptive cytoprotection" mediated by prostaglandins. Am J Physiol. 1983; 245(1):G113-21. DOI: 10.1152/ajpgi.1983.245.1.G113. View

14.

Leung F, Guth P, Scremin O, Golanska E, Kauffman Jr G . Regional gastric mucosal blood flow measurements by hydrogen gas clearance in the anesthetized rat and rabbit. Gastroenterology. 1984; 87(1):28-36. View

15.

Gerkens J, Flexner C, OATES J, SHAND D . Prostaglandin and histamine involvement in the gastric vasodilator action of pentagastrin. J Pharmacol Exp Ther. 1977; 201(2):421-6. View

16.

Lacy E, Ito S . Microscopic analysis of ethanol damage to rat gastric mucosa after treatment with a prostaglandin. Gastroenterology. 1982; 83(3):619-25. View

17.

Yano S, Isobe Y, Harada M . The etiology of caffeine-induced aggravation of gastric lesions in rats exposed to restraint plus water-immersion stress. J Pharmacobiodyn. 1982; 5(7):485-94. DOI: 10.1248/bpb1978.5.485. View

18.

Leung F, Miller J, Guth P . Dissociated effects of misoprostol on gastric acid secretion and mucosal blood flow. Dig Dis Sci. 1986; 31(2 Suppl):86S-90S. DOI: 10.1007/BF01309329. View

19.

Harris J, NIGON K, Alonso D . Adenosine-3',5'-monophosphate: intracellular mediator for methyl xanthine stimulation of gastric secretion. Gastroenterology. 1969; 57(4):377-84. View

20.

Tanaka T, Morioka Y, GEBERT U . Effect of a novel xanthine derivative on experimental ulcers in rats. Arzneimittelforschung. 1993; 43(5):558-62. View