Protection by amylin of gastric erosions induced by indomethacin or ethanol in rats.
1. The effect of amylin on gastric ulcers induced by oral administration of indomethacin (Indo, 20 mg kg-1 at a dosing volume of 5 ml) or ethanol 50% (EtOH, 1 ml/rat) was investigated in conscious rats. 2. Amylin given intracerebroventricularly (0.22, 0.66 and 2.2 micrograms/rat, i.c.v.) demonstrated a dose-dependent cytoprotective effect against both Indo and EtOH-induced ulcers. In contrast, amylin, given subcutaneously at doses effective in inhibiting acid gastric secretion (2.5, 10 and 40 micrograms kg-1, s.c.), did not show any cytoprotective effect. 3. The interaction between amylin and endogenous nitric oxide (NO) in the maintenance of gastric mucosal integrity was investigated by pretreating the rats with a selective inhibitor of NO-synthesis, NG-nitro-L-arginine methyl ester (L-NAME, 25 and 70 mg kg-1, s.c.). Administration of L-NAME to rats did not significantly increase the degree of the Indo-induced ulcer index and was not able to remove the protective effect of amylin on Indo-induced ulcers, thus excluding a role for endogenous NO in mediating the protective effect of this peptide. 4. To determine whether the cytoprotective effect of amylin was mediated by endogenous prostaglandins, we studied the effect of amylin (2.2 micrograms/rat, i.c.v.) on EtOH- induced ulcers in rats pretreated with Indo (10 mg kg-1, s.c.) to inhibit prostanoid biosynthesis; Indo was injected 30 min before amylin and EtOH after a further 30 min. Pretreatment with Indo did not significantly increase the ulcer index induced by EtOH but counteracted the ability of amylin to prevent the ulcer formation. 5. These findings suggest that amylin exerts a gastroprotective activity that is not strictly related to inhibition of acid gastric secretion and can be partly explained through a prostaglandin-dependent mechanism mediated by receptors for the peptide in the brain. Amylin might be considered as a new brain-gut peptide.
Guidobono
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Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy.
Pagani
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Ticozzi
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Sibilia
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V
Pecile
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Netti
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C
D000682:Amyloid / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D058228:Islet Amyloid Polypeptide; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D000431:Ethanol; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin