McLane J, Osber M, Pawelek J M
Biochem Biophys Res Commun. 1987 Jun 15;145(2):719-25. doi: 10.1016/0006-291x(87)91024-2.
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.
左旋多巴是黑色素生成过程中的关键代谢产物。然而，由于它会发生自氧化且在中性pH下相对不溶，因此难以用于生物学实验。多巴磷酸盐在左旋多巴苯丙氨酸环的3位和/或4位含有磷酸酯键，与左旋多巴相比，使其具有高度的溶解性且对自氧化稳定。多巴磷酸盐很容易被培养中的黑色素瘤细胞摄取，并被细胞磷酸酶转化为左旋多巴和无机磷酸盐，这使得它们可用于研究体内左旋多巴的作用。在这里，我们研究了多巴磷酸盐对培养的黑色素瘤细胞中促黑素（MSH）受体的影响。我们发现，多巴磷酸盐使细胞对MSH的结合能力提高了3倍，这可能是由于MSH受体数量增加而受体亲和力没有明显变化所致。对MSH结合能力的增加伴随着细胞酪氨酸酶活性和黑色素生成的增加。因此，多巴磷酸盐和/或左旋多巴可以作为MSH受体系统的调节剂。这些观察结果提示了一种调节激素反应性的新机制：靶途径中的代谢产物对激素信号的放大作用。
