Effects of isopropyl unoprostone on melanogenesis in mouse epidermal melanocytes.
OBJECTIVE
To investigate the effects of isopropyl unoprostone (referred to as unoprostone) on melanin synthesis and the nature of melanin.


METHODS
M1 and M2, potential intraocular oxidized metabolites of unoprostone, were added to the culture medium in a cultured immortal line of mouse epidermal melanocytes, melan-a, once a day for 2 weeks at concentrations of 5 nM and 50 nM. Vehicle solution was utilized as a control. The amounts of pyrrole-2,3,5-tricarboxylic acid (PTCA), an oxidized product of eumelanin, and aminohydroxyphenylalanine (AHP), a hydrolyzed product of pheomelanin, were measured by high-performance liquid chromatography.


RESULTS
A 5-nM concentration of M2 significantly increased PTCA production (20.84 +/- 3.17 ng/10(6) cells mean +/- SD) compared with the control (14.58 +/- 4.62 ng/10(6) cells) (P =.04), although other concentrations did not affect the synthesis of PTCA or AHP. A 5-nM concentration of M2 significantly increased the PTCA/AHP (1.86 +/- 0.18) ratio compared with the control (1.37 +/- 0.41) (P =.04). A 50 nM concentration of M2 slightly increased the PTCA/AHP (1.74 +/- 0.58) ratio, but M1 did not affect this ratio.


CONCLUSIONS
These results indicate that M2 affects not only melanogenesis but also the nature of melanin, which could result in unoprostone-generated iridial pigmentation.
Kashiwagi
K
K
Departments of Ophthalmology, Yamanashi Medical University, Tamaho, Japan.
Tsukamoto
K
K
Wakamatsu
K
K
Itoh
S
S
Suzuki
M
M
Tsukahara
S
S
D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011758:Pyrroles / Q000378:metabolism
D008543:Melanins; D011758:Pyrroles; C018362:pheomelanin; C041877:eumelanin; C072630:isopropyl unoprostone; C071226:pyrrole-2,3,5-tricarboxylic acid; D015237:Dinoprost