三甲喹啉对肥大细胞组胺释放的抑制机制。

Inhibitory mechanism of tritoqualine on histamine release from mast cells.

作者信息

Umezu K, Yuasa S, Ichikawa A

出版信息

Biochem Pharmacol. 1986 Sep 15;35(18):3137-42. doi: 10.1016/0006-2952(86)90398-9.

Abstract

Tritoqualine (TRQ, (+)-(R*)-7-amino-4,5,6-triethoxy-3-[(R*)-5,6,7, 8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[4,5-g]isoquinolin++ +-5-yl] phthalide) strongly inhibited the increased metabolism of [3H]arachidonic acid-labeled phospholipid and 45Ca2+ influx in mast cells stimulated by compound 48/80 (compd 48/80), Concanavalin A (Con A) plus phosphatidylserine (PS), or 2,4-dinitrophenyl-coupled-ascaris extracts (DNP-asc). However, TRQ did not disturb the binding of 14C-labeled compd 48/80 to the mast cell membrane. The activity of calmodulin purified from mastocytoma P-815 cells was inhibited by TRQ at IC50 1.0 microM. From these results, it is concluded that the inhibitory mechanism of TRQ on stimulus-induced histamine release from mast cells may be mediated at least partially by the inhibition of Ca2+ influx and calmodulin activity.

摘要

曲托喹啉（TRQ，(+)-(R*)-7-氨基-4,5,6-三乙氧基-3-[(R*)-5,6,7,8-四氢-4-甲氧基-6-甲基-1,3-二氧杂环戊并[4,5-g]异喹啉-5-基]邻苯二甲酰亚胺）强烈抑制化合物48/80、刀豆球蛋白A（伴刀豆球蛋白A）加磷脂酰丝氨酸（PS）或2,4-二硝基苯基偶联蛔虫提取物（DNP-蛔虫提取物）刺激的肥大细胞中[3H]花生四烯酸标记磷脂的代谢增加和45Ca2+内流。然而，TRQ并不干扰14C标记的化合物48/80与肥大细胞膜的结合。从肥大细胞瘤P-815细胞纯化的钙调蛋白活性被TRQ抑制，IC50为1.0微摩尔。从这些结果得出结论，TRQ对刺激诱导的肥大细胞组胺释放的抑制机制可能至少部分是通过抑制Ca2+内流和钙调蛋白活性介导的。