Catecholamine effects on human melanoma cells evoked by α1-adrenoceptors

The biological effects of catecholamines in mammalian pigment cells are poorly understood. Our previous results showed the presence of α1-adrenoceptors in SK-Mel 23 human melanoma cells. The aims of this work were to (1) characterize catecholamine effects on proliferation, tyrosinase activity and expression, (2) identify the α1- adrenoceptor subtypes, and (3) verify whether chronic norepinephrine (NE) treatment modified the types and/or pharmacological characteristics of adrenoceptors present in SK-Mel 23 human melanoma cells. Cells treated with the aradrenergic agonist, phenylephrine (PHE, 10-5 or 10-4 M), for 24-72 h, exhibited decreased cell proliferation and enhanced tyrosinase activity, but unaltered tyrosinase expression as compared with the control. The proliferation and tyrosinase activity responses were inhibited by the α1-adrenergic antagonist prazosin, suggesting they were evoked by α1-adrenoceptors. The presence of actinomycin D, a transcription inhibitor, did not diminish PHE-induced effects. RT-PCR assays, followed by cloning and sequencing, demonstrated the presence of α1A- and α1B-adrenoceptor subtypes. NE-treated cells (24 or 72 h) were used in competition assays, and showed no significant change in the competition curves of α1-adrenoceptors as compared with control curves. Other adrenoceptor subtypes were not identified in these cells, and NE pretreatment did not induce their expression. In conclusion, the activation of SK-Mel 23 human melanoma α1- radrenoceptors elicit biological effects, such as proliferation decrease and tyrosinase activity increase. Desensitization or expression of other adrenoceptor subtypes after chronic NE treatment were not observed.

Keywords

α1-Adrenoceptors, Catecholamines, Cell proliferation, SK-Mel 23 melanoma cells, Tyrosinase activity, alpha 1 adrenergic receptor, alpha 1 adrenergic receptor blocking agent, alpha 1 adrenergic receptor stimulating agent, ascorbic acid, benoxathian, catecholamine, dactinomycin, monophenol monooxygenase, noradrenalin, phenylephrine, prazosin, adrenergic system, catecholamine metabolism, cell proliferation, cell strain SK Mel 23, controlled study, enzyme activity, human, human cell, melanoma cell, pigment cell, priority journal, reverse transcription polymerase chain reaction, Western blotting, Adrenergic alpha-Agonists, Binding, Competitive, Cell Division, Cell Line, Tumor, Gene Expression, Humans, Melanoma, Monophenol Monooxygenase, Norepinephrine, Phenylephrine, Receptors, Adrenergic, alpha-1, Skin Neoplasms