肌醇脂质和cAMP在血小板活化因子诱导血小板聚集中的作用

Effect of inositol lipid and cAMP on PAF-induced platelet aggregation

目的 :探讨肌醇脂质和cAMP两个细胞内第二信使系统在血小板活化因子 (PAF)诱导血小板聚集过程中所起到的作用和相互关系。方法 :采用PKC激动剂PMA和Ca2 + 通道A2 3 187,以及PKA激动剂Sp cAMPS和抑制剂Rp cAMPS干预的方法 ,分析观察这两个信使系统在PAF诱导血小板聚集过程中的作用 ;采用3 H Inositol和1 4 C Adenine双标记液体闪烁技术测定PAF诱导血小板可逆聚集过程中肌醇 1,4,5 三磷酸酯 (IP3 )和cAMP的水平变化的方法 ,分析研究这两个信使系统在PAF诱导血小板聚集过程中的相互关系。结果 :( 1)PMA和A2 3 187能分别增强PAF的血小板聚集效应 ,而且两者具有协同作用 ;( 2 )Rp cAMP和Sp cAMPS两者本身都不能引起血小板聚集 ,但能分别增强和抑制PAF的聚集效应 ;( 3 )IP3 和cAMP的水平变化分别与血小板的聚集和解聚过程一致。结论 :( 1)肌醇脂质信使系统是细胞内转导PAF诱导血小板聚集的主要胞内信使系统。 ( 2 )降低血小板内cAMP浓度不能诱导聚集 ,但能增强肌醇脂质信使系统的聚集效应 ;升高cAMP水平能拮抗肌醇脂质信使系统的作用 。

Objective:To investigate the effect of two intracellular second messenger systems,inositol lipid and cAMP,on PAF induced platelet aggregation.Methods:PAF induced platelet aggregation and levels of inositol 1,4,5 triphosphate(IP 3)and cAMP during the reversible phase of platelet aggregation were measured by platelet agglutometer and double labeled liquid scintillation technique with 3H inositol and 14 C adenine,respectively.Results:(1)phorbol myristate acetate(PKC agonist)and A23187 (calcium inophore)enhanced the PAF induced platelet aggregation response,and both had a synergistic effect.(2)Rp cAMPS(PKA antagonist)and Sp cAMPS(PKA agonist)promoted and inhibited the PAF induced platelet aggregation response,respectively,but both did not induce the platelet aggregation.(3)The increase and decrease of IP 3 and cAMP contents were related to the platelet aggregation and disaggregation.Conclusion:(1)Inositol lipid system plays a pivotal role in PAF induced platelet aggregation.(2)The decrease of cAMP level in platelets does not induce platelet aggregation,but reinforces the effect of inositol lipid system on platelet aggregation;the increase of cAMP concentration lessens the role of inositol lipid system in platelet aggregation,which could be an important mechanism in the disaggregation of reversible platelet aggregation.