Abstract
The hypothesis that specific protein kinase C (PKC) isoforms regulate dopamine transporter (DAT) function was tested in Xenopus laevis oocytes expressing human (h)DAT. Activation of conventional PKCs (cPKCs) and novel PKCs (nPKCs) using 10 nM phorbol 12-myristate 13-acetate (PMA) significantly inhibited DAT-associated transport currents. This effect was reversed by isoform-non-selective PKC inhibitors, selective inhibitors of cPKCs and deltaPKC, and by Ca2+ chelation. By contrast, the epsilonPKC translocation inhibitor peptide had no effect on PMA-induced inhibition of hDAT transport-associated currents. Thus, the primary mechanism by which PMA regulates hDAT expressed in oocytes appears to be by activating cPKC(s).
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Dopamine Plasma Membrane Transport Proteins
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Enzyme Inhibitors / pharmacology
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Female
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Humans
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In Vitro Techniques
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism
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Membrane Glycoproteins*
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Membrane Transport Modulators
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Membrane Transport Proteins / antagonists & inhibitors
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism*
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Models, Biological
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Nerve Tissue Proteins*
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Oocytes / metabolism
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Tetradecanoylphorbol Acetate / pharmacology
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Xenopus laevis
Substances
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Dopamine Plasma Membrane Transport Proteins
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Enzyme Inhibitors
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Isoenzymes
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Membrane Glycoproteins
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Membrane Transport Modulators
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Recombinant Proteins
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SLC6A3 protein, human
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Protein Kinase C
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Tetradecanoylphorbol Acetate