JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kuratani, K.
Right arrow Articles by Yamaguchi, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kuratani, K.
Right arrow Articles by Yamaguchi, I.

Enhancement of gastric mucosal blood flow by beta-3 adrenergic agonists prevents indomethacin-induced antral ulcer in the rat

K Kuratani, H Kodama and I Yamaguchi

Basic Research Group, Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Ibaraki, Japan.

Indomethacin (32 mg/kg s.c.) produced mainly antral ulcers in refed rats but almost exclusively corpus erosions in fasted rats. Subcutaneous doses of a nonselective beta (isoproterenol), a selective beta-2 (salbutamol) and selective beta-3 adrenergic agonists CBRL35135, (R*,R*)-(+/-)-methyl 4-[2-[2-hydroxy-2-(3- chlorophenyl)ethylamino]propyl] phenoxyacetate hydrobromide; CL316,243, disodium (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxy-ethyl]- amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate; SR58611A, ethyl[(7S)- 7-[(2R)-(2(3-chlorophenyl)-2-hydroxyethylamino]5,6,7, 8- tetrahydronaphthalen-2-yloxy]acetate hydrochloride) dose-dependently attenuated the antral ulcers, and their activities were in the order of BRL35135 (ED50 = 0.03 mg/kg) > CL316,243 (ED50 = 0.04 mg/kg) > SR58611A (ED50 = 0.2 mg/kg) > isoproterenol (ED50 = 0.4 mg/kg) > salbutamol (ED50 = 6 mg/kg). Whereas only isoproterenol, salbutamol and BRL35135 significantly attenuated the corpus erosions and reduced gastric acid secretion in pylorus-ligated rats. In in vitro, all the beta agonists enhanced the beating rate of guinea pig atria (beta-1 action) and inhibited spontaneous contractions of rat uterus (beta-2 action) and colon (beta-3 action). There was found a statistically significant correlation between the IC50 values of the drugs on the colon and ED50 values on the indomethacin-induced antral ulcers (r = 0.97). In addition, the beta agonists excepting salbutamol increased antral gastric mucosal blood flow in rats anesthetized with halothane, and the activities were arranged in the potency order of inhibiting colon motility.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 270, Issue 2, pp. 559-565, 08/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 GutHome page
A Anthony, R E Pounder, A P Dhillon, and A J Wakefield
Vascular anatomy defines sites of indomethacin induced jejunal ulceration along the mesenteric margin
Gut, December 1, 1997; 41(6): 763 - 770.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1994 by the American Society for Pharmacology and Experimental Therapeutics.