Catecholamine effects on human melanoma cells evoked by α1-adrenoceptors
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2004-08-01
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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.
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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
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Archives of Dermatological Research, v. 296, n. 3, p. 112-119, 2004.