Conventional protein kinase C isoforms regulate human dopamine transporter activity in Xenopus oocytes.
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).
Doolen
Suzanne
S
Department of Pharmacology and Neuroscience Program, C-236, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA. suzanne.doolen@uchsc.edu
Zahniser
Nancy R
NR
D000818:Animals; D050483:Dopamine Plasma Membrane Transport Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014982:Xenopus laevis
D050483:Dopamine Plasma Membrane Transport Proteins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C493214:SLC6A3 protein, human; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate