Investigation of the mechanisms involved in the central effects of glucagon-like peptide-1 on ethanol-induced gastric mucosal lesions.
The aim of this study was to investigate the effects of intracerebroventricularly injected glucagon-like peptide-1 (GLP-1) on ethanol-induced gastric mucosal damage and to elucidate the mechanisms involved. Absolute ethanol was administered through an orogastric cannula 5 min before GLP-1 (1 microg/10 microl) injection. One hour later, the rats were decapitated, their stomachs were removed and scored for mucosal damage. GLP-1 inhibited the ethanol-induced gastric mucosal damage by 92%. Centrally injected atropine sulphate, a muscarinic receptor antagonist (5 microg/10 microl), prevented the gastroprotective effect of GLP-1, while mecamylamine, a nicotinic receptor antagonist (25 microg/10 microl), was ineffective. Peripherally injected atropine methyl nitrate (1 mg/kg) did not change the effect of GLP-1, but mecamylamine (5 mg/kg) blocked it. Cysteamine, a somatostatin depletor (280 mg/kg, s.c.), did not affect the protective activity of GLP-1, while inhibition of nitric oxide (NO) synthesis by L-NAME (3 mg/kg, i.v.) significantly abolished the protective effect of GLP-1 on ethanol-induced gastric mucosal lesions. We conclude that central muscarinic and peripheral nicotinic cholinergic receptors and NO, but not somatostatin, contribute to the protective effect of intracerebroventricularly injected GLP-1 on ethanol-induced gastric mucosal damage.
Isbil-Buyukcoskun
Naciye
N
Uludag University Medical Faculty, Department of Physiology, 16059, Gorukle, Bursa, Turkey. nisbil@uludag.edu.tr
Gulec
Guldal
G
D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D003543:Cysteamine / Q000008:administration & dosage / Q000494:pharmacology; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D052216:Glucagon-Like Peptide 1; D007276:Injections, Intraventricular; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D010455:Peptides; D000431:Ethanol; D003543:Cysteamine; D008464:Mecamylamine; D001285:Atropine; D052216:Glucagon-Like Peptide 1