Affolter H, Burkard W P, Pletscher A
Eur J Pharmacol. 1985 Jan 22;108(2):157-62. doi: 10.1016/0014-2999(85)90720-4.
In human blood platelets verapamil and D600 (2-methoxyverapamil) in therapeutic concentrations inhibited the shape change reaction induced by 5-hydroxytryptamine (5HT) but not that induced by ADP. The N-methylated derivatives (D575 and D890) had much less effect. The inhibitory action of verapamil was independent of external Ca2+. Nitrendipine and diltiazem (20 microM) had no effect on the 5HT- and the ADP-induced shape change reactions. Since both these shape change reactions are mediated by a rise in cytoplasmic free Ca2+, it is concluded that the inhibition of the 5HT effect by verapamil and D600 was not due to their interference with calcium channels but rather to an antagonistic action on 5HT2-receptors. This view is supported by the finding that verapamil but not D575 competed with [3H]ketanserin and [3H]spiroperidol for their specific binding sites on membranes of rat cerebral cortex.
在人体血小板中，治疗浓度的维拉帕米和D600（2-甲氧基维拉帕米）可抑制5-羟色胺（5HT）诱导的形态变化反应，但不抑制ADP诱导的形态变化反应。N-甲基化衍生物（D575和D890）的作用则小得多。维拉帕米的抑制作用与细胞外Ca2+无关。尼群地平和地尔硫䓬（20微摩尔）对5HT和ADP诱导的形态变化反应均无影响。由于这两种形态变化反应均由细胞质游离Ca2+浓度升高介导，因此得出结论，维拉帕米和D600对5HT效应的抑制并非因其对钙通道的干扰，而是对5HT2受体的拮抗作用。这一观点得到以下发现的支持：维拉帕米而非D575可与[3H]酮色林和[3H]螺哌啶竞争其在大鼠大脑皮质膜上的特异性结合位点。
