Sildenafil inhibits phosphodiesterase type 5 in human clitoral corpus cavernosum smooth muscle

Kwangsung Park, Robert B. Moreland, Irwin Goldstein, Anthony Atala, Abdulmaged Traish

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Phosphodiesterases play an important physiological role by regulating the intracellular levels of cyclic nucleotides. In this study, we investigated the kinetic parameters of inhibition of phosphodiesterase (PDE) type 5 (EC 3.1.4.35, 3@?,5@?-cyclic GMP phosphodiesterase) by a novel, high-affinity, selective PDE type 5 inhibitor, sildenafil, in intact cells and in soluble extracts of human clitoral corpus cavernosum smooth muscle cells. Sildenafil inhibited cGMP hydrolysis in the crude extract (K(i) = 7.2 ± 2.7) and in partially purified preparations (K(i) = 9 nM) in a competitive manner, as determined by Dixon plots. Sildenafil was a more effective PDE type 5 inhibitor than zaprinast (K(i) = 400.0 ± 76.4 nM, crude extracts; 250 nM, partially purified). Stimulation of intracellular cGMP synthesis by the nitric oxide donor sodium nitroprusside resulted in a 3.3- and 2.9-fold increase in cGMP concentration in the presence of sildenafil or zaprinast, respectively, compared to sodium nitroprusside treatment alone in intact cells at physiological temperatures. These observations suggest that human clitoral corpus cavernosum smooth muscle tone may be regulated by the synthesis and release of nitric oxide and that this pathway is dependent on PDE type 5 activity.

Original languageEnglish
Pages (from-to)612-617
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume249
Issue number3
DOIs
StatePublished - Aug 28 1998
Externally publishedYes

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Keywords

  • cGMP
  • Clitoral corpus cavernosum smooth muscle cells
  • Female sexual dysfunction
  • Phosphodiesterase type 5
  • Sildenafil (Viagra)

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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