Elsevier

Biochemical Pharmacology

Volume 33, Issue 3, 1 February 1984, Pages 453-457
Biochemical Pharmacology

Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle

https://doi.org/10.1016/0006-2952(84)90240-5Get rights and content

Abstract

A novel vasodilating agent, vinpocetine (14-ethoxycarbonyl-(3α, 16α-ethyl-14, 15-eburnamenine) inhibits Ca2+-dependent phosphodiesterase, selectively, among the three forms of cyclic nucleotide phosphodiesterase identified in the rabbit aorta. The concentration of vinpocetine producing 50% inhibition of Ca2+-dependent phosphodiesterase activity was approximately 21 μM, both in the presence and absence of Ca2+-calmodulin (CaM). Increasing the concentration of CaM in the presence of Ca2+ did not prevent vinpocetine-induced inhibition of Ca2+-dependent phosphodiesterase, thereby indicating that vinpocetine inhibited the enzyme by interacting with the enzyme and not with CaM. To determine the influence of vinpocetine-induced inhibition of Ca2+-dependent phosphodiesterase on cyclic nucleotide metabolism in vascular smooth muscle, cyclic nucleotide levels in isolated rabbit aortic strips were also investigated. Addition of vinpocetine produced dose-dependent increases in only the cyclic GMP levels and there was no significant effects on the cyclic AMP levels. These results provide pharmacological evidence that Ca2+-dependent phosphodiesterase mainly hydrolyzes cyclic GMP in vascular smooth muscle. Vinpocetine may induce vascular relaxation by increasing cyclic GMP contents in vascular smooth muscle through selective inhibition of Ca2+-dependent phosphodiesterase.

References (17)

  • H. Hidaka et al.

    Biochim. biophys. Acta

    (1977)
  • H. Hidaka et al.

    Archs Biochem. Biophys.

    (1978)
  • H. Hidaka et al.

    Biochem. Med.

    (1974)
  • T. Asano et al.

    Biochem. biophys. Res. Commun.

    (1977)
  • K. Nakazawa et al.

    Biochim. biophys. Acta

    (1976)
  • K.D. Schultz et al.

    Nature (Lond.)

    (1977)
  • W.R. Kukovetz et al.

    Namyn-Schmiedeberg's Archs Pharmac.

    (1979)
  • C.A. Gruetter et al.

    J. Pharmac. exp. Ther.

    (1981)
There are more references available in the full text version of this article.

Cited by (127)

  • Phosphodiesterase 1 inhibition and molecular docking study of phytochemicals isolated from stem heartwood of Heterophragma adenophyllum Seem

    2020, South African Journal of Botany
    Citation Excerpt :

    These intracellular signals were then relieving vasoconstriction and inflammation through interaction with other kinase enzymes. One of the famous PDE-I inhibitors is vinpocetine (Hagiwara et al., 1984) which is used as a vasodilator (Miyazaki, 1995). Our tested compounds significantly blocked the PDE-I and might be a potential vasodilator and anti-inflammatory.

  • A comprehensive review on the potential therapeutic benefits of phosphodiesterase inhibitors on cardiovascular diseases

    2017, Biomedicine and Pharmacotherapy
    Citation Excerpt :

    In vitro, PDE1A and PDE1B give the impression of having a high specificity for cGMP, whereas PDE1C has similar affinity for both cGMP and cAMP [38,39]. The foremost PDE1 inhibitors are nimodipine [40], vinpocetine [41], IC224 [42], phenothiazines, and SCH51866 [43]. Previously, researchers have realized the lack of information about the presence of PDEs in cardiac myocytes [44] and the nonattendance of specific inhibitors of PDE1 clarifies why there has been little examination of the impacts of PDE1 hindrance in models of CVD.

View all citing articles on Scopus
View full text