The roles of membrane estrogen receptor subtypes in modulating dopamine transporters in PC-12 cells

Rebecca A. Alyea, Stephanie E. Laurence, Sung H. Kim, Benita S. Katzenellenbogen, John A. Katzenellenbogen, Cheryl S. Watson

    Research output: Contribution to journalArticle

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    Abstract

    The effects of 17β-estradiol (E2) on dopamine (DA) transport could explain gender and life-stage differences in the incidence of some neurological disorders. We tested the effects of E2 at physiological concentrations on DA efflux in nerve growth factor-differentiated rat pheochromocytoma cells that express estrogen receptors (ER) α, ERβ, and G-protein coupled receptor 30 (GPR30), and DA transporter (DAT). DAT efflux was determined as the transporter-specific loss of 3H-DA from pre-loaded cells; a 9-15 min 10-9 M E2 treatment caused maximal DA efflux. Such rapid estrogenic action suggests a non-genomic response, and an E2-dendrimer conjugate (limited to non-nuclear actions) caused DA efflux within 5 min. Efflux dose-responses for E2 were non-monotonic, also characteristic of non-genomic estrogenic actions. ERα siRNA knockdown abolished E2-mediated DA efflux, while ERβ knockdown did not, and GPR30 knockdown increased E2-mediated DA efflux (suggesting GPR30 is inhibitory). Use of ER-selective agonists/antagonists demonstrated that ERα is the predominant mediator of E2-mediated DA efflux, with inhibitory contributions from GPR30 and ERβ. E2 also caused trafficking of ERα to the plasma membrane, trafficking of ERβ away from the plasma membrane, and unchanged membrane GPR30 levels. Therefore, ERα is largely responsible for non-genomic estrogenic effects on DAT activity.

    Original languageEnglish (US)
    Pages (from-to)1525-1533
    Number of pages9
    JournalJournal of Neurochemistry
    Volume106
    Issue number4
    DOIs
    StatePublished - Aug 2008

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    Dopamine Plasma Membrane Transport Proteins
    Estrogen Receptors
    Dopamine
    Membranes
    G-Protein-Coupled Receptors
    Cell membranes
    Estrogens
    Cell Membrane
    Dendrimers
    Pheochromocytoma
    Nerve Growth Factor
    Nervous System Diseases
    Small Interfering RNA
    Rats
    Estradiol
    Membrane Proteins
    Incidence

    Keywords

    • 17β-estradiol
    • Dopamine efflux
    • Dose-response
    • Nongenomic
    • Rapid effect

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

    Cite this

    Alyea, R. A., Laurence, S. E., Kim, S. H., Katzenellenbogen, B. S., Katzenellenbogen, J. A., & Watson, C. S. (2008). The roles of membrane estrogen receptor subtypes in modulating dopamine transporters in PC-12 cells. Journal of Neurochemistry, 106(4), 1525-1533. https://doi.org/10.1111/j.1471-4159.2008.05491.x

    The roles of membrane estrogen receptor subtypes in modulating dopamine transporters in PC-12 cells. / Alyea, Rebecca A.; Laurence, Stephanie E.; Kim, Sung H.; Katzenellenbogen, Benita S.; Katzenellenbogen, John A.; Watson, Cheryl S.

    In: Journal of Neurochemistry, Vol. 106, No. 4, 08.2008, p. 1525-1533.

    Research output: Contribution to journalArticle

    Alyea, RA, Laurence, SE, Kim, SH, Katzenellenbogen, BS, Katzenellenbogen, JA & Watson, CS 2008, 'The roles of membrane estrogen receptor subtypes in modulating dopamine transporters in PC-12 cells', Journal of Neurochemistry, vol. 106, no. 4, pp. 1525-1533. https://doi.org/10.1111/j.1471-4159.2008.05491.x
    Alyea RA, Laurence SE, Kim SH, Katzenellenbogen BS, Katzenellenbogen JA, Watson CS. The roles of membrane estrogen receptor subtypes in modulating dopamine transporters in PC-12 cells. Journal of Neurochemistry. 2008 Aug;106(4):1525-1533. https://doi.org/10.1111/j.1471-4159.2008.05491.x
    Alyea, Rebecca A. ; Laurence, Stephanie E. ; Kim, Sung H. ; Katzenellenbogen, Benita S. ; Katzenellenbogen, John A. ; Watson, Cheryl S. / The roles of membrane estrogen receptor subtypes in modulating dopamine transporters in PC-12 cells. In: Journal of Neurochemistry. 2008 ; Vol. 106, No. 4. pp. 1525-1533.
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