Role of calcitonin gene-related peptide and nitric oxide in the gastroprotective effect of capsaicin in the rat

Gastroenterology. 1993 May;104(5):1371-80. doi: 10.1016/0016-5085(93)90345-d.


Background: Capsaicin-sensitive neurons contain various peptides including calcitonin gene-related peptide. This study examines (1) whether calcitonin gene-related peptide is involved in capsaicin-induced gastroprotection and (2) whether nitric oxide and prostaglandin 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, anti-calcitonin gene-related peptide antibodies, and NG-nitro-L-arginine.

Results: Protection by capsaicin was dose-dependently (50% inhibitory dose, 305 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 gene-related 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.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Blood Pressure / drug effects
  • Calcitonin Gene-Related Peptide / immunology
  • Calcitonin Gene-Related Peptide / pharmacology
  • Calcitonin Gene-Related Peptide / physiology*
  • Capsaicin / pharmacology*
  • Gastric Mucosa / drug effects*
  • Indomethacin / pharmacology
  • Male
  • Nitric Oxide / metabolism*
  • Nitroarginine
  • Peptide Fragments / pharmacology
  • Rats
  • Receptors, Calcitonin
  • Receptors, Cell Surface / antagonists & inhibitors
  • Recombinant Proteins
  • Stomach Diseases / chemically induced
  • Stomach Diseases / prevention & control*


  • Antibodies
  • Peptide Fragments
  • Receptors, Calcitonin
  • Receptors, Cell Surface
  • Recombinant Proteins
  • calcitonin gene-related peptide (8-37)
  • Nitroarginine
  • Nitric Oxide
  • Arginine
  • Calcitonin Gene-Related Peptide
  • Capsaicin
  • Indomethacin