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Medline ® Abstract for Reference 72

of 'Treatment of male sexual dysfunction'

72
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PDE5 inhibitor promotes melanin synthesis through the PKG pathway in B16 melanoma cells.
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Zhang X, Yan G, Ji J, Wu J, Sun X, Shen J, Jiang H, Wang H
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J Cell Biochem. 2012 Aug;113(8):2738-43.
 
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.
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Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
PMID