title: Production of prostaglandin e(2) by iridial melanocytes exposed to latanoprost acid, a prostaglandin F(2 alpha) analogue.
abstract: Several prostaglandin analogues used for glaucoma treatment cause increased pigmentation of the iris. The purpose of the present study was investigate whether latanoprost, a PGF(2 alpha) analogue, has any effect on the production of endogenous prostaglandins in iridial melanocytes, which could be important in the mechanism leading to increased pigmentation. Bovine and human iridial melanocytes in culture were used for the experiments. Production of endogenous prostaglandins was measured by enzyme immunoassay, and the melanin content was measured spectrophotometrically. In bovine iridial melanocytes, latanoprost acid caused a significant increase of the PGE(2) production, which could be blocked by indomethacin and NS398, indicating an involvement of cyclo-oxygenase 2. In order to study the selectivity of the phenomenon other endogenous substances/drugs were tested, e.g., acetylcholine, carbachol, noradrenaline, neuropeptide Y, substance P and alpha-MSH, but none was found to have any significant effect. Human iridial melanocytes also responded to latanoprost acid with increased production of PGE(2) and in 1 out of 5 individuals increased melanogenesis coincided with increased PGE(2) production. In bovine iridial melanocytes, latanoprost acid did not stimulate melanogenesis. These results indicate that latanoprost acid cause enhanced formation of endogenous prostaglandins that may have auto- and/or paracrine effects in the melanocytes, possibly associated with melanogenesis.
authors.affiliation: Department of Neuroscience, Unit of Pharmacology, Biomedical Center, Uppsala University, Uppsala, Sweden. kerstin.bergh@neuro.uu.se
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bergh
authors.forename: Parri
authors.initials: P
authors.lastname: Wentzel
authors.forename: Johan
authors.initials: J
authors.lastname: Stjernschantz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D007498:Iris / Q000166:cytology / Q000187:drug effects*; D000077338:Latanoprost; D008297:Male; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000166:cytology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism; D014130:Trabeculectomy
chemical_list: D011461:Prostaglandins F, Synthetic; D013929:Thromboxane B2; D000077338:Latanoprost; D015232:Dinoprostone