Central action of adrenomedullin to prevent ethanol-induced gastric injury through vagal pathways in rats

Adrenomedullin (AM), belongs to the calcitonin gene-related peptide (CGRP) family and interacts with AM and CGRP(1) receptors. Specific AM receptors and immunoreactivity are present in the rat brain. The effect of intracisternal injection of rat AM on ethanol-induced gastric lesions was studied in conscious Wistar rats. The peptide was injected intracisternally or intravenously under short anesthesia 20 min before intragastric injection of 70% ethanol. Corpus lesions were determined 1 h after ethanol. Intracisternal AM (75, 150, and 300 pmol) dose-dependently inhibited ethanol-induced gastric lesions by 40-72% and rat alpha-CGRP (150 pmol ic) by 76%. Intravenous AM (300 pmol) had no effect. The CGRP(1) receptor antagonist CGRP-(8-37) (9.6-19.2 nmol ic) dose-dependently inhibited the protective effect of intracisternal alpha-CGRP but not that of AM. Subdiaphragmatic vagotomy and peripheral injection of atropine, indomethacin, or N-G-nitro-L-arginine methyl ester (L-NAME) prevented AM protective action. L-Arginine but not D-arginine blocked L-NAME action. These data suggest that both AM and CGRP act in the brain to prevent ethanol-induced gastric lesions through interaction with their specific receptors. AM action may involve vagal cholinergic-dependent modulation of prostaglandins and nitric oxide protective mechanisms.