Mechanism of capsaicin-induced relaxation in equine tracheal smooth muscle.
The effects of capsaicin and neuropeptides were examined in equine tracheal smooth muscle (TSM). Neither capsaicin nor substance P (SP) contracted TSM. Capsaicin (100 microM) elicited relaxation in TSM contracted with methacholine. This relaxation was not mimicked by SP or calcitonin gene-related peptide (CGRP). Relaxation was not attenuated by removal of the epithelium or by pretreatment of tissue with meclofenamate or the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine. Previous exposure of TSM to capsaicin did not eliminate the relaxation responses to subsequent capsaicin. Although vasoactive intestinal peptide (VIP) elicited marked relaxation that was attenuated by alpha-chymotrypsin, alpha-chymotrypsin did not affect the capsaicin-induced relaxation. Capsaicin-induced relaxation was abolished by charybdotoxin, a blocker of large-conductance Ca(2+)-activated K+ channels. These results indicate that capsaicin-induced equine TSM relaxation is not mediated either by neuropeptides such as SP or CGRP released from capsaicin-sensitive sensory nerves or by prostanoids, NO, or VIP. Relaxation is due to the effect of capsaicin on large-conductance Ca(2+)-activated K+ channels. The peptidergic nerves play no important role in the regulation of TSM tone in horse airways.
Zhu
F X
FX
Department of Large Animal Clinical Sciences, Michigan State University, East Lansing 48824-1314, USA.
Zhang
X Y
XY
Olszewski
M A
MA
Robinson
N E
NE
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D002918:Chymotrypsin / Q000494:pharmacology; D004847:Epithelial Cells / Q000502:physiology; D006736:Horses; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D013373:Substance P / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D051036:Large-Conductance Calcium-Activated Potassium Channels; D009479:Neuropeptides; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D016210:Methacholine Chloride; D018999:Charybdotoxin; D019335:Nitroarginine; D009569:Nitric Oxide; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D002918:Chymotrypsin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin