Hagiwara M, Endo T, Hidaka H
Nihon Yakurigaku Zasshi. 1982 Oct;80(4):317-23.
Effect of a novel compound, 14-ethoxycarbonyl-(3 alpha, 16 alpha-ethyl)-14,15-eburnamenine (vinpocetine, TCV-3B), on the cyclic nucleotide metabolism and in vitro response of a vascular strip was investigated. The concentration of vinpocetine producing relaxation of the canine basilar arterial strip induced by 30 microM arachidonate peroxide was 3 microM. Cyclic GMP content in the vascular strip increased dose-dependently by addition of vinpocetine, and 2.5-fold elevation of cyclic GMP content in the vascular strip was observed by 10 microM vinpocetine. Administration of vinpocetine concentrations ranging from 1 to 100 microM did not produce a significant increase in cyclic AMP of the vascular strip. Vinpocetine did not stimulate guanylate cyclase, but selectively inhibited Ca2+-calmodulin dependent phosphodiesterase (Ca2+-PDE). Increase in cyclic GMP by vinpocetine is due to inhibition of Ca2+-PDE because Ca2+-PDE is known to hydrolyze cyclic GMP preferentially. Our results suggest that vinpocetine, a selective Ca2+-PDE inhibitor, produces relaxation of the vascular strip by the increase in cyclic GMP.
研究了一种新型化合物14 - 乙氧羰基 -（3α，16α - 乙基）-14,15 - 长春胺（长春西汀，TCV - 3B）对血管条带环核苷酸代谢及体外反应的影响。使30微摩尔花生四烯酸过氧化物诱导的犬基底动脉条带松弛的长春西汀浓度为3微摩尔。通过添加长春西汀，血管条带中的环鸟苷酸（cGMP）含量呈剂量依赖性增加，10微摩尔长春西汀使血管条带中的cGMP含量升高了2.5倍。给予1至100微摩尔浓度范围的长春西汀未使血管条带中的环磷酸腺苷（cAMP）显著增加。长春西汀不刺激鸟苷酸环化酶，但选择性抑制钙 - 钙调蛋白依赖性磷酸二酯酶（Ca2 + - PDE）。长春西汀使cGMP增加是由于抑制了Ca2 + - PDE，因为已知Ca2 + - PDE优先水解cGMP。我们的结果表明，作为一种选择性Ca2 + - PDE抑制剂，长春西汀通过增加cGMP使血管条带松弛。
