{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:32:22Z","timestamp":1778113942582,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,6,15]],"date-time":"2012-06-15T00:00:00Z","timestamp":1339718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010induced 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\u2010CPT\u2010cGMP stimulated CREB phosphorylation, leading to increased tyrosinase expression and melanin synthesis, which was counteracted by KT5823, a selective cGMP\u2010dependent protein kinase (PKG) inhibitor. However, KT5823 did not affect cAMP\u2010elevating agent\u2010mediated melanin synthesis, indicating that KT5823 selectively inhibited cGMP\u2010induced melanin synthesis. This is the first study to find that PDE5 inhibitor can promote melanin synthesis and reveal that PKG\u2010dependent CREB phosphorylation and tyrosinase expression is involved in cGMP\u2010induced melanin synthesis. Our results suggest that PDE5 inhibitor may be beneficial for the treatment of hypopigmentation diseases. J. Cell. 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