Effects of intracerebroventricularly injected glucagon-like peptide-2 on ethanol-induced gastric mucosal damage in rats

ABSTRACT

Purpose: The present study aims to investigate the effects of intracerebroventricularly (i.c.v.)-injected glucagon-like peptide-2 (GLP-2) on ethanol-induced gastric mucosal damage and to reveal the mechanisms involved in this effect.

Materials and Methods: Rats received absolute ethanol orally via an orogastric tube 30 minutes after GLP-2 (1–200 ng/10 µl; i.c.v.) or saline (10 µl) injections. They were decapitated 1 hour later, their stomachs were removed, and the gastric mucosal damage was scored.

Results: A total of 100 ng GLP-2 inhibited the gastric mucosal damage by 67%. This effect was abolished by the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (10 µg/kg; s.c.), but was not affected by either the nitric oxide (NO) synthase inhibitor L-NAME (30 mg/kg; s.c.) or the cyclooxygenase inhibitor indomethacin (5 mg/kg; i.p.). The most effective gastroprotective dose of GLP-2 (100 ng/10 µl; i.c.v.), but not the higher doses (150 or 200 ng/10 µl; i.c.v.) prevented the decrease in gastric mucosal blood flow caused by ethanol.

In conclusion, i.c.v. GLP-2 protects against ethanol-induced gastric mucosal damage and this effect is mediated by CGRP receptor activation and gastric mucosal blood flow, but not by NO or prostaglandins.

KEYWORDS:

• Ethanol
• gastric mucosal damage
• glucagon-like peptide-2
• i.c.v.
• rat

Declaration of interest

The authors declare that they have no conflicts of interest.

Additional information

Funding

This work was supported by the Research Fund of Uludag University Project number [HDP(T)-2012/3].