[The effects of a novel Ca2+ channel blocker, KB-2796, on 5-HT-induced responses].
[The effects of a novel Ca2+ channel blocker, KB-2796, on 5-HT-induced responses].
复制标题
[新型 Ca2 通道阻滞剂 KB-2796 对 5-HT 诱导反应的影响]。
DOI：
10.1254/fpj.104.19
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
T. Sukamoto
中科院分区：
文献类型：
--
作者：
Y. Fujishima;H. Hara;M. Shimazawa;K. Yokota;T. Sukamoto
本文以维拉帕米、氟桂利嗪、地尔硫卓、尼莫地平等钙通道阻断剂为对照，观察了新型钙通道阻断剂KB-2796对5-羟色胺（5-HT）诱发的反应的影响。在大鼠皮层膜中，KB-2796以竞争性方式抑制特异性[3 H]螺哌隆与5-HT 2受体的结合（Ki = 0.57 μ M），但在10或100 μ M浓度下，对放射性配体与其他5-HT受体亚型（如5-HT 1、5-HT 1A、5-HT 1B、5-HT 1C和5-HT 3）的结合表现出可忽略不计的亲和力。KB-2796抑制5-HT刺激的形状变化以及5-HT和胶原蛋白刺激的兔富血小板血浆聚集，IC 50值分别为13.4 μ M和96.4 μ M。KB-2796还抑制5-HT诱导的兔血小板[Ca 2 +]i升高，IC 50值为25.7 μ M。此外，KB-2796（3-30 mg/kg，p.o.）剂量依赖性地抑制5-HT诱导的大鼠足肿胀。KB-2796和其他钙通道阻滞剂的抑制作用与它们对5-HT_2受体的亲和力有关，KB-2796的抑制作用强于地尔硫卓和尼莫地平，与氟桂利嗪相当，尽管它们的抑制作用都弱于维拉帕米。提示KB-2796对5-HT_2受体具有拮抗作用。
The effects of KB-2796, a new Ca(2+)-channel blocker, on 5-hydroxytryptamine (5-HT)-induced responses were investigated in comparison with those of other Ca(2+)-channel blockers such as verapamil, flunarizine, diltiazem and nimodipine. In rat cortical membrane, KB-2796 inhibited specific [3H]spiperone binding to 5-HT2 receptors in a competitive manner (Ki = 0.57 microM), but exhibited negligible affinity for radioligand binding to other 5-HT receptor subtypes such as 5-HT1, 5-HT1A, 5-HT1B, 5-HT1C and 5-HT3 at a concentration of 10 or 100 microM. KB-2796 inhibited both 5-HT-stimulated shape change and 5-HT and collagen-stimulated aggregation in rabbit platelet-rich plasma with IC50 values of 13.4 microM and 96.4 microM, respectively. KB-2796 also inhibited the 5-HT-induced increase of [Ca2+]i in washed rabbit platelets with the IC50 value of 25.7 microM. Furthermore, KB-2796 (3-30 mg/kg, p.o.) dose-dependently inhibited the 5-HT-induced paw edema in rats. In these experiments, the inhibitory effects of KB-2796 and other Ca2+ channel blockers were related to their affinities for the 5-HT2 receptor; and the potency of KB-2796 was stronger than those of diltiazem and nimodipine and almost equal to that of flunarizine, although all these inhibitors had weaker potencies than that of verapamil. These findings indicate that KB-2796 may possess antagonistic effect on the 5-HT2 receptor.