title: PDE5 inhibitor promotes melanin synthesis through the PKG pathway in B16 melanoma cells.
abstract: 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.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Guirui
authors.initials: G
authors.lastname: Yan
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.forename: Jingwei
authors.initials: J
authors.lastname: Wu
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Sun
authors.forename: Jingshan
authors.initials: J
authors.lastname: Shen
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Heyao
authors.initials: H
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D008543:Melanins / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008543:Melanins; D058986:Phosphodiesterase 5 Inhibitors; D014442:Monophenol Monooxygenase