Protection by gastrin in the rat stomach involves afferent neurons, calcitonin gene-related peptide, and nitric oxide

Gastroenterology
T StroffB A Peskar

Abstract

Certain gut peptides exert gastroprotective effects. However, the underlying mechanism is not fully understood. This study examines the contribution of afferent neurons, calcitonin gene-related peptide, and nitric oxide to the protection conferred by gastrin 17 in the rat stomach. Gastroprotection by gastrin 17 against ethanol-induced gross and histological damage was studied after capsaicin-induced defunctionalization of afferent neurons, pretreatment with the calcitonin gene-related peptide receptor antagonist human calcitonin gene-related peptide8-37, anti-calcitonin gene-related peptide antibodies, and the NO synthase inhibitor NG-nitro-L-arginine. Gastrin 17 (1-25 pmol/kg) dose-dependently prevented mucosal damage caused by ethanol. Protection was inhibited by functional ablation of afferent neurons or pretreatment with human calcitonin gene-related peptide8-37 (50% inhibitory dose, 86 pmol.kg-1.min-1), anticalcitonin gene-related peptide antibodies, or NG-nitro-L-arginine (50% inhibitory dose, 1 mg/kg). L-Arginine but not D-arginine reversed the effect of NG-nitro-L-arginine. Effects on gross damage were paralleled by histology. Protective doses of gastrin 17 increased gastric mucosal blood flow and, in addition, elevated...Continue Reading

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