RESEARCH ARTICLE


Protective Effect of Tegaserod Against Indomethacin-Induced Gastric Injury in the Rat



Kalina Venkovab, David L. Earnest c, Beverley Greenwood-Van Meerveld a, b, *
a VA Medical Center, Oklahoma City, OK 73104, USA
b Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, 921 NE 13th Street, Oklahoma City, OK 73104, USA
c Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA

Article Information


Identifiers and Pagination:

Year: 2008
Volume: 2
First Page: 10
Last Page: 16
Publisher Id: TOPHARMJ-2-10
DOI: 10.2174/1874143600802010010

Article History:

Received Date: 10/01/2008
Revision Received Date: 22/01/2008
Acceptance Date: 29/01/2008
Electronic publication date: 12/2/2008
Collection year: 2008

© 2008 Venkova et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, 921 NE 13th Street, Oklahoma City, OK 73104, USA; Tel: 405-270-0501, Ext. 3547; Fax: 405-290-1719; E-mail: Beverley-Greenwood@ouhsc.edu


Abstract

Gastric contractions induced by non-steroidal anti-inflammatory drugs (NSAIDs) contribute to mucosal ulceration. The goal of the present study was to investigate whether maintaining normal gastric motility provides protection against NSAIDs. A rat model of indomethacin-induced gastric mucosal injury and muscle hypercontratility was used to evaluate the protective effect of pretreatment with the 5-HT4 receptor agonist tegaserod (1 mg/kg b.i.d.) in comparison to the effect of the proton pump inhibitor omeprazole (20 mg/kg b.i.d). Indomethacin induced mucosal ulceration associated with hypercontractility of isolated antral muscle strips in response to KCl, carbachol, 5-HT or electrical field stimulation. Pretreatment with tegaserod alone or in combination with omeprazole prevented both mucosal ulceration and muscle hypercontractility. In contrast, omeprazole protected the mucosa without preventing the development of muscle hypercontractility. The results show that activation of peripheral 5-HT4 receptors promotes normal contractility of the antrum suggesting a different mechanism of gasrtoprotection against NSAIDs.