Inhibition of nitric oxide synthesis blocks the inhibitory response to capsaicin in intestinal circular muscle preparations from different species.
Moderate concentrations of the sensory stimulant drug capsaicin caused relaxation in human and animal intestinal circular muscle preparations (guinea-pig proximal, mouse distal colon, human small intestine and appendix) in vitro. With the exception of the guinea-pig colon, the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine (L-NOARG; 10(-4) M) strongly inhibited the relaxant effect of capsaicin. Tetrodotoxin, an inhibitor of voltage-sensitive Na+ channels failed to significantly reduce the inhibitory effect of capsaicin in the guinea-pig colon, human ileum and appendix; it caused an approximately 50% reduction in the mouse colon. The relaxant effect of capsaicin was strongly reduced in colonic preparations from transient receptor potential vanilloid type (TRPV1) receptor knockout mice as compared to their wildtype controls. It is concluded that nitric oxide, possibly of sensory origin, is involved in the relaxant action of capsaicin in the circular muscle of the mouse and human intestine.
Benko
Rita
R
Department of Pharmacology and Pharmacotherapy, University Medical School of Pecs, Szigeti ut 12, H-7643 Pecs, Hungary.
Lazar
Zsofia
Z
Undi
Sarolta
S
Illenyi
Laszlo
L
Antal
Andras
A
Horvath
Ors-Peter
OP
Rumbus
Zoltan
Z
Wolf
Matyas
M
Maggi
Carlo A
CA
Bartho
Lorand
L
D000818:Animals; D002211:Capsaicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003106:Colon / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology*
D019335:Nitroarginine; D013779:Tetrodotoxin; D019001:Nitric Oxide Synthase; D002211:Capsaicin