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Effects of tachykinin receptor antagonists on leukotriene C-4-induced bronchoconstriction and airway microvascular leakage in guinea pigs



Effects of tachykinin receptor antagonists on leukotriene C-4-induced bronchoconstriction and airway microvascular leakage in guinea pigs



Zhongguo Yaolixue Yu Dulixue Zazhi 11(1): 11-13



The involvement of endogenous tachykinins in the airway actions of leukotriene C-4(LTC-4) was studied. LTC-4 (0.5 mu-g cntdot kg-1, iv) increased intrapulmonary pressure (IPP) and extravasation of Evans blue in the airways in guinea pigs. CP-96345 ((2S,3S)-cis-2-(diphenylmethyl)-N((2-methoxyphenyl)-methyl)-1-azabicyclo(2.2.2)octane-3-amine), a NK-1 tachykinin receptor antagonist (1 mg cntdot kg-1, iv) attenuated LTC-4-induced increase of Evans blue extravasation in the airways, and SR-48968 ( (S)-N-methyl-N-(4-(4-acetylamino-4-phenylpiperidino)-2-(3, 4-dichlorophenyl) butyl) benzamide) , a NK-2 receptor antagonist (1 mg cntdot kg-1, iv) inhibited increase in IPP, respectively. ONO-1078 (0.03 mg cntdot kg-1, iv), a leukotriene antagonist, decreased both responses. The results indicate that endogenous tachykinins potentiate the responses of LTC-4 on airways, microvascular leakage mediated by NK-1 receptors, and bronchoconstriction by NK-2 receptors.

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