Inoue T, Sohma R, Morooka S
Department of Cardiology, Koshigaya Hospital, Dokkyo University School of Medicine, Koshigaya City, Saitama, Japan.
Thromb Res. 1999 Feb 1;93(3):137-43. doi: 10.1016/s0049-3848(98)00172-8.
Cilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Our study was designed to investigate inhibitory effects of cilostazol on the expression of activation-dependent platelet membrane surface glycoproteins. We performed flow cytometric analysis using monoclonal antibodies, PAC-1 (antibody against activation dependent epitope of GPIIb/IIIa), anti-CD62P (P-selectin), and anti-CD63. In vitro ADP stimulation of platelets taken from seven healthy volunteers produced significant increases in the mean channel fluorescence intensities (MFI) for PAC-1 (148% increase) and CD62P (43% increase) but did not increase in that for CD63. The enhanced MFI for CD62P was suppressed to the control level by pretreatment with 1 microM (88% suppression), 3 microM (94% suppression), and 10 microM (95% suppression) of cilostazol. However, that of PAC-1 was suppressed to a lesser degree (12, 16, and 21% suppressions, respectively). Cilostazol may inhibit P-selectin release from alpha-granule, rather than activation-dependent conformational change of GPIIb/IIIa in platelets. Cilostazol inhibits cellular interaction among platelets, leukocytes, and vascular endothelial cells mediated by P-selectin.
西洛他唑是一种新开发的抗血小板药物，已广泛应用于临床。其抗血小板作用似乎主要与抑制细胞内磷酸二酯酶活性有关。我们的研究旨在探讨西洛他唑对活化依赖性血小板膜表面糖蛋白表达的抑制作用。我们使用单克隆抗体PAC-1（抗GPIIb/IIIa活化依赖性表位抗体）、抗CD62P（P-选择素）和抗CD63进行流式细胞术分析。体外对7名健康志愿者的血小板进行ADP刺激后，PAC-1的平均通道荧光强度（MFI）显著增加（增加148%），CD62P的MFI也显著增加（增加43%），但CD63的MFI没有增加。用1μM（抑制88%）、3μM（抑制94%）和10μM（抑制95%）的西洛他唑预处理可将CD62P增强的MFI抑制至对照水平。然而，PAC-1的MFI抑制程度较小（分别为12%、16%和21%的抑制率）。西洛他唑可能抑制α-颗粒中P-选择素的释放，而不是血小板中GPIIb/IIIa的活化依赖性构象变化。西洛他唑抑制由P-选择素介导的血小板、白细胞和血管内皮细胞之间的细胞相互作用。
