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 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 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 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.
Department of Experimental Clinical Medicine, Ruhr-University of Bochum, Germany.
N
N
Lambrecht
M
M
Burchert
M
M
Respondek
K M
KM
Müller
B M
BM
Peskar
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins; D013272:Stomach Diseases / Q000139:chemically induced / Q000517:prevention & control*
D000906:Antibodies; D010446:Peptide Fragments; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C058636:calcitonin gene-related peptide (8-37); D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D007213:Indomethacin