Fennessy M R, Stewart A G, Thompson D C
Br J Pharmacol. 1986 Apr;87(4):741-9. doi: 10.1111/j.1476-5381.1986.tb14592.x.
The effects of leukotrienes C4 and D4 (LTC4 and LTD4), administered intravenously or by aerosol, on the bronchoconstrictor potency of intravenously administered histamine have been investigated in anaesthetized, mechanically ventilated guinea-pigs. LTC4 (2 nM) had no effect on either the EC50 or the maximum contractile response to histamine on the isolated trachea of the guinea-pig. At 10 nM, LTC4 induced a rightward shift in the histamine concentration-response curve without affecting the maximum response. LTD4 (0.05-0.20 nmol kg-1, i.v.) dose-dependently enhanced histamine (9-36 nmol kg-1, i.v.)-induced increases in airways resistance, whereas equibronchoconstrictor doses of LTC4 (0.1-0.4 nmol kg-1, i.v.), failed to enhance histamine-induced increases in airways resistance. Aerosols of LTC4 and LTD4 generated from solutions of 1-16 microM and administered for 30 s, elicited concentration-dependent bronchoconstrictions comprising decreases in dynamic compliance and increases in airways resistance. At 20 min after exposure to these aerosols, the potency of histamine (9-36 nmol kg-1, i.v.) was significantly increased on both airways resistance and dynamic compliance. The potentiation induced by LTC4 (4 microM, 30 s) was maintained up to 60 min after aerosol exposure whereas that induced by LTD4 (4 microM, 30 s) was maintained up to 40 min after aerosol exposure but was not significantly different (P greater than 0.05, unpaired Student's t test) to saline-exposed animals at 60 min. LTC4 as has been previously reported for LTD4, does not enhance the histamine-induced contraction of isolated airways smooth muscle. In contrast to LTD4, intravenously administered LTC4 does not appear to enhance histamine-induced bronchoconstriction. On the other hand, aerosols of either LTC4 or LTD4 potentiate histamine in vivo in a concentration-dependent manner. These data suggest that leukotrienes may contribute to the regulation of airways reactivity to histamine in the guinea-pig.
在麻醉、机械通气的豚鼠中，研究了静脉注射或雾化给予白三烯C4和D4（LTC4和LTD4）对静脉注射组胺支气管收缩效力的影响。LTC4（2 nM）对豚鼠离体气管对组胺的半数有效浓度（EC50）或最大收缩反应均无影响。在10 nM时，LTC4使组胺浓度-反应曲线右移，但不影响最大反应。LTD4（0.05 - 0.20 nmol kg-1，静脉注射）剂量依赖性地增强组胺（9 - 36 nmol kg-1，静脉注射）诱导的气道阻力增加，而等支气管收缩剂量的LTC4（0.1 - 0.4 nmol kg-1，静脉注射）未能增强组胺诱导的气道阻力增加。由1 - 16 microM溶液产生并给予30 s的LTC4和LTD4气雾剂，引起浓度依赖性支气管收缩，包括动态顺应性降低和气道阻力增加。在暴露于这些气雾剂20分钟后，组胺（9 - 36 nmol kg-1，静脉注射）对气道阻力和动态顺应性的效力均显著增加。LTC4（4 microM，30 s）诱导的增强作用在气雾剂暴露后长达60分钟维持，而LTD4（4 microM，30 s）诱导的增强作用在气雾剂暴露后长达40分钟维持，但在60分钟时与盐水暴露动物无显著差异（P大于0.05，未配对学生t检验）。如先前报道的LTD4一样，LTC4不会增强组胺诱导的离体气道平滑肌收缩。与LTD4相反，静脉注射的LTC4似乎不会增强组胺诱导的支气管收缩。另一方面，LTC4或LTD4气雾剂在体内以浓度依赖性方式增强组胺作用。这些数据表明，白三烯可能参与豚鼠气道对组胺反应性的调节。
