alpha-Methyl-p-tyrosine inhibits latanoprost-induced melanogenesis in vitro.
The PGF2alpha derivative, latanoprost, is a recent anti-glaucoma drug that has been reported to induce a discrete incidence of increased iris pigmentation in men. The present experiments were made in order to study whether this phenomenon could be influenced by the tyrosinase inhibitor, alpha-methyl-p-tyrosine. Melanin content, melanin production and tyrosinase activity of cultured uveal melanocytes derived from irides of brown or brown-blue color were measured after adding latanoprost at different molar concentration with or without alpha-methyl-p-tyrosine (10(-5)m). It was shown that latanoprost stimulated melanin content, melanin production and tyrosinase activity in a molar range between 10(-7) and 10(-5)m in uveal melanocytes derived from irides of both brown and brown-blue color. The effect seemed to be more pronounced in melanocytes derived from irides of brown-blue color. The adding of alpha-methyl-p-tyrosine completely prevented latanoprost-induced stimulation of melanin production in uveal melanocytes derived from irides of both colors. These results suggest that latanoprost-induced stimulation of melanin production, follows the metabolic pathway involving tyrosinase activity and may be relevant for the therapeutic application of latanoprost in glaucoma in order to reduce its side-effect resulting in increased iris pigmentation.
Drago
F
F
Institute of Pharmacology, University of Catania Medical School, Catania, Italy.
Marino
A
A
La Manna
C
C
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005127:Eye Color; D006801:Humans; D000077338:Latanoprost; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D011461:Prostaglandins F, Synthetic / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014602:Uvea / Q000187:drug effects / Q000378:metabolism; D019805:alpha-Methyltyrosine / Q000494:pharmacology*