速激肽受体拮抗剂对白三烯C4诱导豚鼠气道收缩和微血管渗漏的作用

本实验探讨了内源性速激肽是否参与白三烯C₄(LTC₄)的气道效应. LTC₄(0.5 μg·kg^-1, iv)可增高豚鼠肺内压(IPP)和气道内依文思蓝渗出。速激肽NK-1受体拮抗剂CP-96345｛(2S, 3S)-顺式-2-( 二苯甲基)-N-［(2-甲氧苯)-甲基］-1-杂氮双环［2.2.2］辛烷-3-胺｝ 1 mg·kg^-1，iv，可减弱LTC₄诱导的依文思蓝渗出；NK-2受体拮抗剂SR-48968｛(S)-N-甲基-N-［4-(4-乙酰氨基-4-苯基哌啶)-2-(3,4-二氯苯基)丁基］苯甲酰胺｝，1 mg·kg^-1， iv，可抑制IPP的增高. 白三烯拮抗剂ONO-1078 (0.03 mg·kg^-1, iv)可阻断这两种反应. 结果说明内源性速激肽增强 LTC₄的气道作用，其中NK-1受体介导微血管渗漏，NK-2受体介导支气管收缩.

Effects of tachykinin receptor antagonists on leukotriene C4-  induced bronchoconstriction and airway microvascular leakage in guinea pigs

The involvement of endogenous tachykinins in the airway actions of leukotriene C₄ (LTC₄) was studied. LTC₄ (0.5 μg·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·kg^-1, iv) attenuated LTC₄-induced increase of Evans blue extravasation in the airways, and SR- 48968 ｛(S)-N-methyl-N-［4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichloro-phenyl) butyl］ benzamide｝, a NK-2 receptor antagonist (1 mg·kg^-1, iv) inhibited increase in IPP, respectively. ONO-1078 (0.03 mg·kg^-1, iv), a leukotriene antagonist, decreased both responses. The results indicate that endogenous tachykinins potentiate the responses of LTC₄ on airways, microvascular leakage mediated by NK-1 receptors, and bronchoconstriction by NK-2 receptors.