title: Central effects of glucagon-like peptide-1 on cold-restraint stress-induced gastric mucosal lesions.
abstract: OBJECTIVE
  Intracerebroventricular (i.c.v.) 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.v. 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.v. 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 microl; i.c.v.) was injected 5 min before cold-restraint stress induction. Rats were pretreated with exendin-(9-39) (2.5 ng/10 microl; i.c.v. and 250 ng/kg; intraperitoneal [i.p.]), calcitonin gene-related peptide (CGRP)-(8-37) (10 microg/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 microl; 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 cold-restraint stress via the activation of its specific receptors, and CGRP, nitric oxide and prostaglandins, but not cholinergic muscarinic receptors, mediate this effect.
authors: Department of Physiology, Uludağ University, School of Medicine, Bursa. nisbil@uludag.edu.tr
authors: Naciye
authors: N
authors: Işbil Büyükcoşkun
authors: Güldal
authors: G
authors: Güleç
authors: Betül
authors: B
authors: Cam Etöz
authors: Kasim
authors: K
authors: Ozlük
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D003080:Cold Temperature; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000503:physiopathology; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D054795:Incretins / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007267:Injections; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D054795:Incretins; D010276:Parasympatholytics; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); C083773:exendin (9-39); D001285:Atropine; D052216:Glucagon-Like Peptide 1; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin