美吡拉敏抑制血小板活化因子诱导的兔血小板聚集：细胞内组胺的作用。

Mepyramine inhibits platelet activating factor-induced rabbit platelet aggregation: role of intracellular histamine.

作者信息

Zeng S, Guo Z G

机构信息

Laboratory of Molecular Pharmacology, Hunan Medical University, Changsha, China.

出版信息

Zhongguo Yao Li Xue Bao. 1997 Mar;18(2):155-8.

PMID:10072970

Abstract

AIM

To study the possible role of intracellular histamine (HA) in platelet activating factor (PAF)-induced platelet activation.

METHODS

Washed rabbit platelet suspension was used to test the inhibitory effect of mepyramine (Mep, an H1 receptor antagonist) on PAF-induced platelet aggregation. The thromboxane B2 (TXB2) generation was measured by radioimmunoassay and the intracellular calcium ([Ca2+]i) concentration was determined by the specific fluorescence indicator Fura-2.

RESULTS

Mep > 100 mumol.L-1 generated a concentration-dependent inhibition on PAF-induced aggregation, with an IC50 value of 162 (95% confidence limits: 114-232 mumol.L-1). Cimetidine, an H2 receptor antagonist, even up to 400 mumol.L-1 had no effect on it. Exogenous HA (10 mumol.L-1) and H1 receptor agonist, 2-thiazolylethylamine had no energetic effect. alpha-Fluoromethylhistidine, an inhibitor of histidine decarboxylase, did not inhibit platelet responses. However, in platelets permeabilized with saponin (8-10 mg.L-1), exogenous HA attenuated the inhibitory effect of Mep to about 50% at a concentration of 50 mumol.L-1. Preincubation of platelets with Mep (100 or 200 mumol.L-1) resulted in an inhibition on TXB2 generation and [Ca2+]i elevation induced by PAF.

CONCLUSION

Platelets activated by PAF is associated with an intracellular HA synthesis and release via a common pathway of TXB2 generation and the rise of [Ca2+]i.

摘要

目的

研究细胞内组胺（HA）在血小板活化因子（PAF）诱导的血小板活化中可能发挥的作用。

方法

采用洗涤后的兔血小板悬液，检测美吡拉敏（Mep，一种H1受体拮抗剂）对PAF诱导的血小板聚集的抑制作用。通过放射免疫分析法测定血栓素B2（TXB2）的生成量，并用特异性荧光指示剂Fura-2测定细胞内钙（[Ca2+]i）浓度。

结果

Mep>100μmol·L-1对PAF诱导的聚集产生浓度依赖性抑制，IC50值为162（95%置信限：114 - 232μmol·L-1）。H2受体拮抗剂西咪替丁即使高达400μmol·L-1也对此无影响。外源性HA（10μmol·L-1）和H1受体激动剂2-噻唑基乙胺无明显作用。组氨酸脱羧酶抑制剂α-氟甲基组氨酸不抑制血小板反应。然而，在用皂苷（8 - 10mg·L-1）通透处理的血小板中，外源性HA在浓度为50μmol·L-1时可将Mep的抑制作用减弱约50%。血小板预先与Mep（100或200μmol·L-1）孵育可抑制PAF诱导的TXB2生成和[Ca2+]i升高。