Effect of ONO-1078, a leukotriene antagonist, on capsaicin- and substance P-induced bronchoconstriction and airway microvascular leakage in guinea pigs.
OBJECTIVE
To study the effect of 4-oxo-8-[p-(4-phenylbutyloxy) benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate (ONO-1078), a specific leukotriene antagonist, on capsaicin (Cap)-sensitive sensory nerve functions in the airways, and clarify the modulating roles of endogenous peptido-leukotrienes.


METHODS
Changes in intrapulmonary pressure (IPP), Evans blue extravasation in airways, and contraction of bronchial smooth muscles of guinea pigs induced by Cap, substance P (SP) and leukotriene C4 (LTC4) were observed.


RESULTS
Cap (0.05 mg.kg-1, i.v.), SP (1 microgram.kg-1, i.v.) and LTC4 (0.5 microgram.kg-1, i.v.) enhanced IPP, and Evans blue extravasation in bronchi and intrapulmonary airways. ONO-1078 0.03 mg.kg-1, i.v. completely blocked the responses to LTC4, attenuated those to Cap, but had no effect to SP. In isolated bronchial smooth muscles, ONO-1078 (1 mumol.L-1) inhibited the contractile response to Cap, but not to SP.


CONCLUSIONS
ONO-1078 partly inhibits Cap-sensitive sensory nerve actions in airways, but has no direct effect on SP, a sensory neuropeptide.
Wei
E Q
EQ
Laboratory of Neurobiology, Zhejiang Medical University, Hangzhou, China.
Liu
J W
JW
Zhang
L F
LF
Zhang
W P
WP
Bian
R L
RL
D000818:Animals; D001980:Bronchi / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin / Q000037:antagonists & inhibitors*; D002867:Chromones / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D013373:Substance P / Q000037:antagonists & inhibitors*
D002867:Chromones; D017997:Leukotriene C4; D013373:Substance P; D002211:Capsaicin; C047681:pranlukast