Tanaka T, Ishikawa T, Hagiwara M, Onoda K, Itoh H, Hidaka H
Department of Molecular and Cellular Pharmacology, Mie University School of Medicine, Japan.
Pharmacology. 1988;36(5):313-20. doi: 10.1159/000138400.
The effects of cilostazol (OPC-13013, 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quin olinone) on cyclic nucleotide metabolism and Ca2+-induced contraction of intact and skinned rabbit arterial smooth muscles were investigated. The concentrations of cilostazol producing 50% inhibition of cyclic adenosine monophosphate phosphodiesterase and Ca2+-dependent cyclic nucleotide phosphodiesterase were 0.4 microM and above 100 microM, respectively. This compound has no significant effect on adenylate cyclase in concentrations of up to 100 microM. Addition of cilostazol increased significantly the cAMP content without significant effect on cyclic guanosine monophosphate level of rabbit thoracic aorta in the presence of forskolin. Moreover, the ED50 value of cilostazol in relaxation of rabbit mesenteric arterial strips was decreased selectively by addition of 0.01 microM forskolin, which alone at this concentration has no effect on vascular contraction. Cilostazol of up to 30 microM did not suppress the Ca2+-induced contraction of the chemically skinned rabbit mesenteric artery. Therefore, cilostazol may produce the relaxation of intact vascular smooth muscle by its inhibition of cyclic adenosine monophosphate hydrolysis.
研究了西洛他唑（OPC - 13013，6 - [4 - (1 - 环己基 - 1H - 四氮唑 - 5 - 基)丁氧基]-3,4 - 二氢 - 2(1H)-喹啉酮）对完整和去皮的兔动脉平滑肌环核苷酸代谢及钙诱导收缩的影响。产生50%抑制环磷酸腺苷磷酸二酯酶和钙依赖性环核苷酸磷酸二酯酶的西洛他唑浓度分别为0.4微摩尔/升和高于100微摩尔/升。该化合物在浓度高达100微摩尔/升时对腺苷酸环化酶无显著影响。在存在福斯可林的情况下，添加西洛他唑可显著增加兔胸主动脉的环磷酸腺苷含量，而对环磷酸鸟苷水平无显著影响。此外，添加0.01微摩尔/升福斯可林可选择性降低西洛他唑对兔肠系膜动脉条舒张的半数有效剂量值，该浓度的福斯可林单独使用时对血管收缩无影响。高达30微摩尔/升的西洛他唑不抑制化学去皮的兔肠系膜动脉的钙诱导收缩。因此，西洛他唑可能通过抑制环磷酸腺苷水解而使完整的血管平滑肌舒张。
