ROLE OF CALCITONIN GENE-RELATED PEPTIDE AND NITRIC-OXIDE IN THE GASTROPROTECTIVE EFFECT OF CAPSAICIN IN THE RAT

Background: Capsaicin-sensitive neurons contain various peptides including calcitonin gene-related peptide. This study examines (1) whether calcitonin generelated peptide is involved in capsaicin-induced gastroprotection and (2) whether nitric oxide and prostaglandins are required for calcitonin gene-related peptide to prevent mucosal injury. Methods: Gastroprotection by capsaicin or calcitonin gene-related peptide against ethanol-induced gross and histological damage was studied after pretreatment with the calcitonin gene-related peptide receptor antagonist, human calcitonin gene-related peptide8-37, anticalcitonin gene-related peptide antibodies, and NG-nitro-l-arginine. Results: Protection by capsaicin was dose-dependently (50% inhibitory dose, 305 pmol · kg-1 · min-1) antagonized by human calcitonin gene-related peptide8-37 and significantly attenuated by anti-calcitonin gene-related peptide antibodies. NG-nitro-l-arginine dose-dependently inhibited the protective effect of calcitonin gene-related peptide (50% inhibitory dose, 0.9 mg/kg), 3 mg/kg completely blocking protection. l-Arginine reversed the effects of NG-nitro-l-arginine. Protection by calcitonin gene-related peptide was neither associated with increased prostaglandin formation nor inhibited by indomethacin. Conclusions: The results suggest that calcitonin generelated peptide is an essential mediator of the protection elicited by stimulation of capsaicin-sensitive neurons and that the protective effect of calcitonin gene-related peptide is lost after blockade of the nitric oxide system but not the prostaglandin system. © 1993.