Phosphorylated isomers of L-dopa stimulate MSH binding capacity and responsiveness to MSH in cultured melanoma cells.
L-dopa is a key metabolite in the process of melanogenesis. However, it is difficult to use in biological experiments because it is subject to auto-oxidation and relatively insoluble at neutral pH. Dopa phosphates contain phosphate ester linkages at positions 3 and/or 4 of the phenylalanine ring of L-dopa, rendering them highly soluble and stable to auto-oxidation when compared to L-dopa. Dopa phosphates are readily taken up by melanoma cells in culture and converted to L-dopa and inorganic phosphate by cellular phosphatases, making them useful for studying L-dopa effects in vivo. Here we investigated the effects of dopa phosphates on receptors for MSH in cultured melanoma cells. We found that dopa phosphates caused a 3-fold stimulation of MSH binding capacity by the cells which probably occurred through an increase in the number of receptors for MSH with no apparent change in affinity of the receptors. The increased binding capacity for MSH was followed by increased cellular tyrosinase activity and melanogenesis. Thus dopa phosphates and/or L-dopa can act as regulators of the MSH receptor system. The observations suggest a novel mechanism for regulation of hormonal responsiveness: hormonal signal amplification by a metabolite in the target pathway.
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007536:Isomerism; D007980:Levodopa / Q000494:pharmacology*; D008543:Melanins / Q000032:analysis; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010766:Phosphorylation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D008543:Melanins; D007980:Levodopa; D009074:Melanocyte-Stimulating Hormones; D014446:Tyrosine 3-Monooxygenase; D014442:Monophenol Monooxygenase