Inhibition of melanization in human melanoma cells by a serotonin uptake inhibitor.
Significant levels of intracellular catecholamines were found in a human melanoma cell line and were enhanced by increasing the extracellular tyrosine concentration. Intracellular dopa, 5-cysteinyldopa, tyrosinase, and melanin also rose under these conditions. 5-HT (serotonin) was synthesized by the melanoma cells but further study was hindered by the high level of 5-HT in fetal calf serum. A 5-HT uptake antagonist, DU 24565 (6-nitroquipazine), was employed as an alternative method for studying 5-HT action. This compound, which in contrast to tunicamycin had no inhibitory effects on cell proliferation or tyrosinase activity, strongly inhibited melanization and decreased the levels of dopa, 5-cysteinyldopa, dopamine, noradrenaline, adrenaline, and 3,4-dihydroxyphenylacetic acid. DU 24565 had little effect on 5-HT or tyrosine accumulation in these cells but suppressed the uptake of extracellular dopa. The results show that human melanoma cells synthesize a wide range of biogenic amines in culture and suggest a new approach to regulating intracellular levels of dopa and of a variety of dopa products.
D002395:Catecholamines / Q000378:metabolism; D002460:Cell Line; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D006801:Humans; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D011804:Quinolines; D011814:Quipazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014443:Tyrosine / Q000378:metabolism / Q000494:pharmacology
D002395:Catecholamines; D008543:Melanins; D011804:Quinolines; D012702:Serotonin Antagonists; D012701:Serotonin; D014443:Tyrosine; D011814:Quipazine; D004295:Dihydroxyphenylalanine; C031227:6-nitroquipazine