Central effects of glucagon-like peptide-1 on cold-restraint stress-induced gastric mucosal lesions

Bueyuekcoskun N., Guelec G., Etoez B. C., Oezluek K.

TURKISH JOURNAL OF GASTROENTEROLOGY, vol.18, no.3, pp.150-156, 2007 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 18 Issue: 3
  • Publication Date: 2007
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.150-156
  • Keywords: glucagon-like peptide-1, intracerebroventricular, gastroprotection, exendin-(9-39), CGRP-(8-37), L-NAME, indomethacin, atropine, RAT-BRAIN, GENE-EXPRESSION, MESSENGER-RNAS, GLP-1, RECEPTOR, EXENDIN-4, ULCERS, VASOPRESSIN, NEURONS, SYSTEM
  • Bursa Uludag University Affiliated: Yes


Background/aims: Intracerebroventricular glucagon-like peptide-1 (GLP-1) has been shown to prevent gastric mucosal lesions induced by reserpine and ethanol. Here, we aimed to investigate the effects of i.c.u. GLP-1 on stress-induced gastric mucosal lesions and the mechanisms which may mediate these effects. Methods: Rats were equipped with intravenous and i.c.u. cannulas under ether anesthesia. To induce cold-restraint stress, rats were kept individually in wire cages, specifically prepared according to their sizes, at 7-9 degrees C for 5 hours. They were then decapitated, and their stomachs were removed and scored for mucosal damage. GLP-1 (1, 10, 100,.1000 ng/10 mu l; i.c.v.) was injected 5 min before cold-restraint stress induction. Rats were pretreated with exendin-(9-39) (2.5 ng/10 mu l; i.c.v. and 2.50 ng/kg; intraperitoneal [i.p.]), calcitonin gene-related peptide (CGRP)-(8-37) (10 mu g/kg; i.p.), N-G-nitro-L-arginine methyl ester (L-NAME) (3 mg/kg; i.v.), indomethacin (5 mg/kg; i.p.) and atropine (1 mg/kg; i.p.) to investigate mechanisms which may mediate the gastroprotective effect of GLP-1. Results: GLP-1 (1000 ng/10 mu l; i.c.v.) significantly prevented gastric mucosal lesions induced by cold-restraint stress (p<0.01). Intracerebroventricular (i.c.v.), but not i.p., injection of exendin-(9-39) significantly blocked the gastroprotective effect of the peptide (p<0.05). Pretreatment with CGRP-(8-37), L-NAME and indomethacin also prevented the gastroprotective effect of i.c.v. GLP-1 (p<0.05, p<0.05 and p<0.01, respectively), while pretreatment with atropine did not prevent the gastroprotective effect of the peptide. Conclusions: We conclude that i.c.v GLP-1 inhibits the gastric mucosal damage induced by coldrestraint stress via the activation of its specific receptors, and CGRP, nitric oxide and prostaglandins, but not cholinergic muscarinic receptors, mediate this effect.