氮䓬斯汀对培养的气道平滑肌细胞内钙离子的作用。

Action of azelastine on intracellular Ca2+ in cultured airway smooth muscle.

作者信息

Senn N, Jeanclos E, Garay R

机构信息

Inserm, Hôpital Necker, Paris, France.

出版信息

Eur J Pharmacol. 1991 Nov 19;205(1):29-34. doi: 10.1016/0014-2999(91)90766-j.

DOI:10.1016/0014-2999(91)90766-j

PMID:1687465

Abstract

Azelastine, a novel antiasthmatic/antiallergic agent, was tested for Ca2+ antagonistic properties in cultured rabbit airway smooth muscle, vascular smooth muscle and cardiocytes. In airway smooth muscle cells, the basal cytosolic free calcium content was 195 +/- 72 nM (mean +/- S.D., n = 18). These basal values were decreased by azelastine with an IC50 value of 1.1 +/- 0.3 x 10(-4) M. Endothelin-1 (10(-7) M) induced a rapid increase in free cytosolic calcium up to 806 +/- 314 nM, which returned to normal levels in 3-5 min. This was fully blocked by azelastine in a concentration-dependent manner, with an IC50 value of 6.7 +/- 2.9 x 10(-5) M. Moreover, azelastine fully blocked histamine-induced calcium mobilization (IC50 = 7 x 10(-5) M). In cultured vascular smooth muscle cells and cardiocytes, azelastine was unable to decrease the basal cytosolic free calcium content or inhibit agonist-induced calcium mobilization. Therefore, at therapeutic levels, a specific, mild inhibition of calcium mobilization in airway smooth muscle may be one component of the antiasthmatic action of azelastine.

摘要

氮卓斯汀是一种新型抗哮喘/抗过敏药物，我们在培养的兔气道平滑肌、血管平滑肌和心肌细胞中对其钙拮抗特性进行了测试。在气道平滑肌细胞中，基础胞浆游离钙含量为195±72 nM（平均值±标准差，n = 18）。氮卓斯汀可降低这些基础值，IC50值为1.1±0.3×10⁻⁴ M。内皮素-1（10⁻⁷ M）可使游离胞浆钙迅速增加至806±314 nM，并在3 - 5分钟内恢复至正常水平。氮卓斯汀可呈浓度依赖性完全阻断这一过程，IC50值为6.7±2.9×10⁻⁵ M。此外，氮卓斯汀可完全阻断组胺诱导的钙动员（IC50 = 7×10⁻⁵ M）。在培养的血管平滑肌细胞和心肌细胞中，氮卓斯汀无法降低基础胞浆游离钙含量或抑制激动剂诱导的钙动员。因此，在治疗水平上，对气道平滑肌钙动员的特异性轻度抑制可能是氮卓斯汀抗哮喘作用的一个组成部分。