PDE5 inhibitor promotes melanin synthesis through the PKG pathway in B16 melanoma cells

J Cell Biochem. 2012 Aug;113(8):2738-43. doi: 10.1002/jcb.24147.


PDE inhibitors could increase cellular cGMP levels and are used to treat erectile dysfunction as well as pulmonary arterial hypertension. cGMP production was reported to be necessary for UVB-induced melanin synthesis, however, the effect of PDE5 inhibitor on melanin synthesis has not been examined. We found that PDE5 inhibitor (sildenafil or vardenafil) and the cGMP analog 8-CPT-cGMP stimulated CREB phosphorylation, leading to increased tyrosinase expression and melanin synthesis, which was counteracted by KT5823, a selective cGMP-dependent protein kinase (PKG) inhibitor. However, KT5823 did not affect cAMP-elevating agent-mediated melanin synthesis, indicating that KT5823 selectively inhibited cGMP-induced melanin synthesis. This is the first study to find that PDE5 inhibitor can promote melanin synthesis and reveal that PKG-dependent CREB phosphorylation and tyrosinase expression is involved in cGMP-induced melanin synthesis. Our results suggest that PDE5 inhibitor may be beneficial for the treatment of hypopigmentation diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Humans
  • Melanins / metabolism*
  • Melanoma, Experimental / metabolism
  • Monophenol Monooxygenase / metabolism
  • Phosphodiesterase 5 Inhibitors / pharmacology*
  • Signal Transduction / drug effects


  • Melanins
  • Phosphodiesterase 5 Inhibitors
  • Monophenol Monooxygenase