학술논문

TLQP-21, a VGF-Derived Peptide, Prevents Ethanol-Induced Gastric Lesions: Insights into Its Mode of Action.
Document Type
Article
Source
Neuroendocrinology. Oct2010, Vol. 92 Issue 3, p189-197. 9p. 1 Illustration, 1 Chart, 6 Graphs.
Subject
*PEPTIDES
*GASTROINTESTINAL motility
*LABORATORY rats
*GASTRIC mucosa
*ETHANOL
*THERAPEUTICS
Language
ISSN
0028-3835
Abstract
Background and Aim: TLQP-21, a peptide derived from the vgf gene, has been reported to play a role in the regulation of rat gastric motility, but its influence on gastric mucosal integrity is unknown. Experimental Approach: We investigated the effects of central (0.8-8 nmol/rat) or peripheral (48-240 nmol/kg) TLQP-21 administration on ethanol- (EtOH, 50%, 1 ml/rat) induced gastric lesions in the rat. The mechanisms involved in such activity were also examined. Results: Central TLQP-21 injection dose-dependently reduced EtOH-induced gastric lesions (ED50 = 3.16 nmol), while peripheral TLQP-21 administration had no effect. The TLQP-21 gastroprotective effect against EtOH injury was accompanied by a significant increase in gastric prostaglandin E2 (PGE2) production linked to an increase in constitutive cyclooxygenase (COX) expression. The nitric oxide (NO) synthase inhibitor L-NAME (70 mg/kg, s.c.), the nonselective COX inhibitor indomethacin (10 mg/kg, orally) and capsaicin denervation removed TLQP-21 gastroprotection. Conclusions: This study shows for the first time that central TLQP-21 exerts a protective action on the gastric mucosa exposed to the noxious agent EtOH. TLQP-21 gastroprotection is mediated by constitutive-derived NO and PGE2, and requires the integrity of sensory nerve fibers. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]