Protective effect of centrally-injected glucagon-like peptide-1 on reserpine-induced gastric mucosal lesions in rat: possible mechanisms.
OBJECTIVE
Intracerebroventricular glucagon-like peptide- 1 (GLP-1) has been shown to prevent the gastric mucosal lesions induced by reserpine. In the present study, we aimed to investigate the contribution of 1- the cholinergic pathway, 2- the sympathetic pathway, 3- somatostatin and 4- endogenous nitric oxide to this gastroprotective effect.


METHODS
Rats were equipped with intravenous and intracerebroventricular cannulas under ether anesthesia for drug delivery. Rats were pretreated with mecamylamine (5 mg/kg; i.p.) and atropine sulfate (1 mg/kg; i.p.), yohimbine (1 mg/kg; i.p.), cysteamine (280 mg/kg; s.c.), and NG-nitro-L-arginine methyl ester (3 mg/kg; i.v.) to investigate the role of the cholinergic pathway, sympathetic pathway, somatostatin and endogenous nitric oxide, respectively, in the gastroprotective effect of GLP-1. To produce gastric mucosal lesions, reserpine was administered intraperitoneally at a dose of 25 mg/kg in 10 ml/kg of 0.5% acetic acid solution. Four hours later, the animals were decapitated, and their stomachs were removed and scored for mucosal damage.


RESULTS
Glucagon- like peptide-1 (100 ng/10 microl; i.c.v.) inhibited the reserpine-induced gastric mucosal damage by 90% (p<0.01). Neither the nicotinic receptor antagonist mecamylamine (5 mg/kg; i.p.) nor the muscarinic receptor antagonist atropine sulfate (1 mg/kg; i.p) affected the gastroprotective activity of GLP-1. On the other hand, pretreatment with yohimbine, an alpha2-adrenergic receptor antagonist (1 mg/kg; i.p.), cysteamine, a somatostatin depletor (280 mg/kg; s.c.), and NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor (3 mg/kg; i.v.), significantly abolished the protective effect of GLP-1 on reserpine-induced gastric mucosal lesions (p<0.001, p<0.01 and p<0.01, respectively).


CONCLUSIONS
We conclude that the sympathetic pathway, somatostatin and nitric oxide, but not the cholinergic pathway, contribute to the gastroprotective effect of intra-cerebroventricular GLP-1 on reserpine-induced gastric mucosal lesions.
Işbil Büyükcoşkun
Naciye
N
Department of Physiology, Uludağ University Medical Faculty, Bursa, Turkey. nisbil@uludag.edu.tr
Güleç
Güldal
G
Ozlük
Kasim
K
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects; D000818:Animals; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000009:adverse effects; D013004:Somatostatin / Q000502:physiology; D013276:Stomach Ulcer / Q000517:prevention & control*; D013564:Sympathetic Nervous System / Q000503:physiopathology
D018759:Adrenergic Uptake Inhibitors; D009569:Nitric Oxide; D013004:Somatostatin; D052216:Glucagon-Like Peptide 1; D012110:Reserpine