Low doses of trh analog act in the dorsal motor nucleus to induce
gastric protection in rats.
Kato, Kimitoshi, Hong Yang, and Yvette Tach[acute]e.
Gastroenteric Biology Center/Digestive Disease Division, West Los
Angeles Veterans Administration Medical Center, Department of
Medicine and Brain Research Institute, University of California Los
Angeles, Los Angeles, California, California 90073
APStracts 2:0175R, 1995.
Mechanisms involved in central TRH analog, RX 77368-induced prevention
of gastric lesions was investigated in urethane-anesthetized rats.
Gastric lesions were induced by intragastric administration of
ethanol (4 ml/kg) and assessed 1 h later by macroscopic visualization
using computerized image analysis. RX 77368 (3, 5, and 10 ng)
microinjected into the dorsal motor nucleus of the vagus (DMN)
decreased ethanol-induced gastric lesions by 79%, 68%, and 61%
respectively. RX 77368 at 1.5, 15 or 30 ng into the DMN or at 3 or 10
ng into the nucleus tractus solitarius, hypoglossal nucleus or
reticular field was ineffective in preventing mucosal damage. The
protective effect of RX 77368 (3 ng into the DMN) was partly
inhibited by peripheral injection of indomethacin and completely
blocked by atropine, the calcitonin gene-related peptide antagonist,
CGRP8-37 and NG-nitro-L-arginine methyl ester (L-NAME). L-arginine,
but not D-arginine reversed the effect of L-NAME. RX 77368 (3 ng into
the DMN) enhanced gastric PGE2 release. These data indicate that low
doses of TRH analog act in the DMN to induce gastric protection
against ethanol injury through muscarinic, PGE2, CGRP and NO
dependent mechanisms.
Received 17 January 1995; accepted in final form 12 June 1995.
APS Manuscript Number R26-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.