PROTECTION BY GASTRIN IN THE RAT STOMACH INVOLVES AFFERENT NEURONS, CALCITONIN-GENE-RELATED PEPTIDE, AND NITRIC-OXIDE

Background & Aims: Certain gut peptides exert gastroprotective effects . However, the underlying mechanism is not fully understood. This stud y examines the contribution of afferent neurons, calcitonin gene-relat ed peptide, and nitric oxide to the protection conferred by gastrin 17 in the rat stomach. Methods: Gastroprotection by gastrin 17 against e thanol-induced gross and histological damage was studied after capsaic in-induced defunctionalization of afferent neurons, pretreatment with the calcitonin gene-related peptide receptor antagonist human calciton in gene-related peptide(8-37), anti-calcitonin gene-related peptide an tibodies, and the NO synthase inhibitor N-G-nitro-L-arginine. Results: Gastrin 17 (1-25 pmol/kg) dose-dependently prevented mucosal damage c aused by ethanol. Protection was inhibited by functional ablation of a fferent neurons or pretreatment with human calcitonin gene-related pep tide(8-37) (50% inhibitory dose, 86 pmol . kg(-1). min(-1)), anticalci tonin gene-related peptide antibodies, or N-G-nitvo-L-arginine (50% in hibitory dose, 1 mg/kg). L-Arginine but not D-arginine reversed the ef fect of N-G-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 plasma gastrin concentrations t o the same extent as intragastric peptone perfusion. Conclusions: Gast rin 17 has potent gastroprotective activity that involves afferent neu rons, calcitonin gene-related peptide, and NO.