Chiu P J, Tetzloff G, Ahn H S, Sybertz E J
Department of Pharmacology, Schering-Plough Corporation, Bloomfield, NJ 07003.
Am J Hypertens. 1988 Jul;1(3 Pt 1):262-8. doi: 10.1093/ajh/1.3.262.
Vinpocetine is a highly specific inhibitor of calmodulin-dependent phosphodiesterase (CaM-PDE) with an IC50 of 19 microM and produces a significant accumulation of cyclic GMP but not cyclic AMP in rabbit aorta. In isolated rabbit aortic strips, vinpocetine (0.01 and 0.1 mM) inhibited the contraction and 45Ca uptake due to both phenylephrine (1 microM) and KCl (40 mM), whereas 8-Br-cyclic GMP (0.1-1mM) selectively impaired phenylephrine-induced responses. Furthermore, the KCl-stimulated 45Ca efflux in normal Ca2+ buffer, which reflects elevated cytosolic Ca2+, was greatly diminished by vinpocetine but not by 8-Br-cyclic GMP. However, phenylephrine-induced 45Ca efflux and contraction in Ca2+-free buffer, which reflect Ca2+ release from intracellular sites, were similarly inhibited by both vinpocetine and 8-Br-cyclic GMP. The results suggest that vinpocetine may effect vasodilatation through blockade of the slow channel and selective inhibition of CaM-PDE in the vascular smooth muscle.
长春西汀是一种对钙调蛋白依赖性磷酸二酯酶（CaM-PDE）具有高度特异性的抑制剂，其半数抑制浓度（IC50）为19微摩尔，可使兔主动脉中的环鸟苷酸（cGMP）显著蓄积，但不会使环磷酸腺苷（cAMP）蓄积。在离体兔主动脉条中，长春西汀（0.01和0.1毫摩尔）抑制了去氧肾上腺素（1微摩尔）和氯化钾（40毫摩尔）引起的收缩及45钙摄取，而8-溴环鸟苷酸（0.1 - 1毫摩尔）则选择性地削弱了去氧肾上腺素诱导的反应。此外，在正常钙离子缓冲液中，氯化钾刺激的45钙外流反映了胞质钙离子升高，长春西汀可使其大幅减少，而8-溴环鸟苷酸则无此作用。然而，在无钙缓冲液中，去氧肾上腺素诱导的45钙外流和收缩反映了细胞内位点的钙释放，长春西汀和8-溴环鸟苷酸对其均有类似的抑制作用。结果表明，长春西汀可能通过阻断慢通道和选择性抑制血管平滑肌中的CaM-PDE来实现血管舒张作用。
