Melatonin receptors in human uveal melanocytes and melanoma cells

Previous work has demonstrated that melatonin inhibits growth of cultured h uman uveal melanoma cells. The goal of this study was to determine the expr ession of mRNA encoding the melatonin receptor subtypes and the effect of s pecific melatonin receptor agonists on cell growth of uveal melanoma cells and melanocytes. RNA expression of the human melatonin Mel(1a) and Mel(1b) receptor subtypes was determined by reverse transcription-polymerase chain reaction (RT-PCR) amplification of RNA isolated from two melanoma cell line s and from one cell line of normal melanocytes. PCR-amplified cDNA encoding the Mel(1b) melatonin receptor subtype, but not the Mel(1a) subtype, was d etected in reverse-transcribed RNA obtained from both normal uveal melanocy tes and melanoma cell lines. Uveal melanoma cells and melanocytes were cult ured for 24 hr, then melatonin or one of its membrane receptor agonists, 6- chloromelatonin (Mel(1a-1b)) or S-20098 (Mel(1b)) or its putative nuclear a gonist, CGP-52608 (Mel(2)), was added to the medium. After 5 days, the cell s were detached, counted, and compared to untreated controls. Melatonin and its membrane receptor agonists (Mel(1a-1b) and Mel(1b)), but not its putat ive nuclear receptor agonist (Mel(2)), inhibited the growth of uveal melano ma cells, but not normal melanocytes, at very low concentrations. In uveal melanoma cells, the expression of RNA encoding the Mel(1b) receptor suggest s that the growth inhibiting effect of melatonin on uveal melanoma cells is related to activation of the melatonin Mel(1b) membrane receptor. Furtherm ore, the expression of RNA encoding melatonin receptors in normal uveal mel anocytes suggests that melatonin may play a role in the function of these c ells.