Creese B R, Bach M K
Prostaglandins Leukot Med. 1983 Jun;11(2):161-9. doi: 10.1016/0262-1746(83)90016-1.
The interactions of leukotriene C4 (LTC4) and D4 (LTD4) with histamine and acetylcholine in contracting guinea pig isolated tracheal smooth muscle have been investigated. In a bathing solution containing 2.5 mM Ca2+, threshold concentrations of the leukotrienes did not affect contractile responses of the smooth muscle to other agonists. However, at a low extracellular Ca2+ concentration (0.1 mM), LTD4 (10(-8) M and 10(-7) M) significantly enhanced contractions induced by histamine or acetylcholine. LTD4 (10(-7) M) shifted the concentration-response curves of these agents leftward by 0.27 and 0.46 log units respectively. The potentiating action of LTD4 was inhibited by the leukotriene antagonist FPL 55712 (3 X 10(-6) M), and was only partially reversible by washing. A subthreshold concentration of potassium chloride (1.5 X 10(-2) M) also increased the sensitivity of the tracheal muscle to acetylcholine in low Ca2+ medium, and this effect was not additive to that of LTD4. These results demonstrate that leukotrienes can alter the in vitro reactivity of airways smooth muscle to other bronchoconstrictor agents. The mechanism of this action may involve altered membrane binding or fluxes of Ca2+, associated with decreased resting potential of the plasma membrane of smooth muscle cells.
已对白三烯C4（LTC4）和D4（LTD4）与组胺及乙酰胆碱在豚鼠离体气管平滑肌收缩过程中的相互作用进行了研究。在含有2.5 mM Ca2+的浴液中，白三烯的阈浓度不影响平滑肌对其他激动剂的收缩反应。然而，在低细胞外Ca2+浓度（0.1 mM）下，LTD4（10^(-8) M和10^(-7) M）显著增强了组胺或乙酰胆碱诱导的收缩。LTD4（10^(-7) M）使这些药物的浓度-反应曲线分别向左移动0.27和0.46个对数单位。LTD4的增强作用被白三烯拮抗剂FPL 55712（3×10^(-6) M）抑制，且仅通过冲洗部分可逆。阈下浓度的氯化钾（1.5×10^(-2) M）也增加了低Ca2+培养基中气管肌肉对乙酰胆碱的敏感性，且该作用与LTD4的作用无相加性。这些结果表明，白三烯可改变气道平滑肌对其他支气管收缩剂的体外反应性。这种作用机制可能涉及与平滑肌细胞质膜静息电位降低相关的膜结合改变或Ca2+通量变化。
