Nongenomic mechanisms of physiological estrogen-mediated dopamine efflux

Rebecca A. Alyea, Cheryl S. Watson

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    Abstract

    Background: Neurological diseases and neuropsychiatric disorders that vary depending on female life stages suggest that sex hormones may influence the function of neurotransmitter regulatory machinery such as the dopamine transporter (DAT). Results: In this study we tested the rapid nongenomic effects of several physiological estrogens [estradiol (E2), estrone (E1), and estriol (E3)] on dopamine efflux via the DAT in a non-transfected, NGF-differentiated, rat pheochromocytoma (PC12) cell model that expresses membrane estrogen receptors (ERs) α, β, and GPR30. We examined kinase, ionic, and physical interaction mechanisms involved in estrogenic regulation of the DAT function. E2-mediated dopamine efflux is DAT-specific and not dependent on extracellular Ca2+-mediated exocytotic release from vesicular monoamine transporter vesicles (VMATs). Using kinase inhibitors we also showed that E2-mediated dopamine efflux is dependent on protein kinase C and MEK activation, but not on PI3K or protein kinase A. In plasma membrane there are ligand-independent associations of ERα and ERβ (but not GPR30) with DAT. Conditions which cause efflux (a 9 min 10-9 M E2 treatment) cause trafficking of ERα (stimulatory) to the plasma membrane and trafficking of ERβ (inhibitory) away from the plasma membrane. In contrast, E1 and E3 can inhibit efflux with a nonmonotonic dose pattern, and cause DAT to leave the plasma membrane. Conclusion: Such mechanisms explain how gender biases in some DAT-dependent diseases can occur.

    Original languageEnglish (US)
    Article number59
    JournalBMC Neuroscience
    Volume10
    DOIs
    StatePublished - Jun 16 2009

    Fingerprint

    Dopamine Plasma Membrane Transport Proteins
    Dopamine
    Estrogens
    Estrogen Receptors
    Cell Membrane
    Phosphotransferases
    Vesicular Monoamine Transport Proteins
    Sexism
    Estriol
    Estrone
    PC12 Cells
    Mitogen-Activated Protein Kinase Kinases
    Gonadal Steroid Hormones
    Pheochromocytoma
    Nerve Growth Factor
    Cyclic AMP-Dependent Protein Kinases
    Phosphatidylinositol 3-Kinases
    Protein Kinase C
    Neurotransmitter Agents
    Estradiol

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience
    • Neuroscience(all)

    Cite this

    Nongenomic mechanisms of physiological estrogen-mediated dopamine efflux. / Alyea, Rebecca A.; Watson, Cheryl S.

    In: BMC Neuroscience, Vol. 10, 59, 16.06.2009.

    Research output: Contribution to journalArticle

    Alyea, Rebecca A. ; Watson, Cheryl S. / Nongenomic mechanisms of physiological estrogen-mediated dopamine efflux. In: BMC Neuroscience. 2009 ; Vol. 10.
    @article{aa697c35db5c456dbd004ff6cb9c252b,
    title = "Nongenomic mechanisms of physiological estrogen-mediated dopamine efflux",
    abstract = "Background: Neurological diseases and neuropsychiatric disorders that vary depending on female life stages suggest that sex hormones may influence the function of neurotransmitter regulatory machinery such as the dopamine transporter (DAT). Results: In this study we tested the rapid nongenomic effects of several physiological estrogens [estradiol (E2), estrone (E1), and estriol (E3)] on dopamine efflux via the DAT in a non-transfected, NGF-differentiated, rat pheochromocytoma (PC12) cell model that expresses membrane estrogen receptors (ERs) α, β, and GPR30. We examined kinase, ionic, and physical interaction mechanisms involved in estrogenic regulation of the DAT function. E2-mediated dopamine efflux is DAT-specific and not dependent on extracellular Ca2+-mediated exocytotic release from vesicular monoamine transporter vesicles (VMATs). Using kinase inhibitors we also showed that E2-mediated dopamine efflux is dependent on protein kinase C and MEK activation, but not on PI3K or protein kinase A. In plasma membrane there are ligand-independent associations of ERα and ERβ (but not GPR30) with DAT. Conditions which cause efflux (a 9 min 10-9 M E2 treatment) cause trafficking of ERα (stimulatory) to the plasma membrane and trafficking of ERβ (inhibitory) away from the plasma membrane. In contrast, E1 and E3 can inhibit efflux with a nonmonotonic dose pattern, and cause DAT to leave the plasma membrane. Conclusion: Such mechanisms explain how gender biases in some DAT-dependent diseases can occur.",
    author = "Alyea, {Rebecca A.} and Watson, {Cheryl S.}",
    year = "2009",
    month = "6",
    day = "16",
    doi = "10.1186/1471-2202-10-59",
    language = "English (US)",
    volume = "10",
    journal = "BMC Neuroscience",
    issn = "1471-2202",
    publisher = "BioMed Central",

    }

    TY - JOUR

    T1 - Nongenomic mechanisms of physiological estrogen-mediated dopamine efflux

    AU - Alyea, Rebecca A.

    AU - Watson, Cheryl S.

    PY - 2009/6/16

    Y1 - 2009/6/16

    N2 - Background: Neurological diseases and neuropsychiatric disorders that vary depending on female life stages suggest that sex hormones may influence the function of neurotransmitter regulatory machinery such as the dopamine transporter (DAT). Results: In this study we tested the rapid nongenomic effects of several physiological estrogens [estradiol (E2), estrone (E1), and estriol (E3)] on dopamine efflux via the DAT in a non-transfected, NGF-differentiated, rat pheochromocytoma (PC12) cell model that expresses membrane estrogen receptors (ERs) α, β, and GPR30. We examined kinase, ionic, and physical interaction mechanisms involved in estrogenic regulation of the DAT function. E2-mediated dopamine efflux is DAT-specific and not dependent on extracellular Ca2+-mediated exocytotic release from vesicular monoamine transporter vesicles (VMATs). Using kinase inhibitors we also showed that E2-mediated dopamine efflux is dependent on protein kinase C and MEK activation, but not on PI3K or protein kinase A. In plasma membrane there are ligand-independent associations of ERα and ERβ (but not GPR30) with DAT. Conditions which cause efflux (a 9 min 10-9 M E2 treatment) cause trafficking of ERα (stimulatory) to the plasma membrane and trafficking of ERβ (inhibitory) away from the plasma membrane. In contrast, E1 and E3 can inhibit efflux with a nonmonotonic dose pattern, and cause DAT to leave the plasma membrane. Conclusion: Such mechanisms explain how gender biases in some DAT-dependent diseases can occur.

    AB - Background: Neurological diseases and neuropsychiatric disorders that vary depending on female life stages suggest that sex hormones may influence the function of neurotransmitter regulatory machinery such as the dopamine transporter (DAT). Results: In this study we tested the rapid nongenomic effects of several physiological estrogens [estradiol (E2), estrone (E1), and estriol (E3)] on dopamine efflux via the DAT in a non-transfected, NGF-differentiated, rat pheochromocytoma (PC12) cell model that expresses membrane estrogen receptors (ERs) α, β, and GPR30. We examined kinase, ionic, and physical interaction mechanisms involved in estrogenic regulation of the DAT function. E2-mediated dopamine efflux is DAT-specific and not dependent on extracellular Ca2+-mediated exocytotic release from vesicular monoamine transporter vesicles (VMATs). Using kinase inhibitors we also showed that E2-mediated dopamine efflux is dependent on protein kinase C and MEK activation, but not on PI3K or protein kinase A. In plasma membrane there are ligand-independent associations of ERα and ERβ (but not GPR30) with DAT. Conditions which cause efflux (a 9 min 10-9 M E2 treatment) cause trafficking of ERα (stimulatory) to the plasma membrane and trafficking of ERβ (inhibitory) away from the plasma membrane. In contrast, E1 and E3 can inhibit efflux with a nonmonotonic dose pattern, and cause DAT to leave the plasma membrane. Conclusion: Such mechanisms explain how gender biases in some DAT-dependent diseases can occur.

    UR - http://www.scopus.com/inward/record.url?scp=67650511672&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=67650511672&partnerID=8YFLogxK

    U2 - 10.1186/1471-2202-10-59

    DO - 10.1186/1471-2202-10-59

    M3 - Article

    VL - 10

    JO - BMC Neuroscience

    JF - BMC Neuroscience

    SN - 1471-2202

    M1 - 59

    ER -