Differential sensitivity of the short and long human dopamine D2 receptor subtypes to protein kinase C

Ya Fang Liu, Olivier Civelli, David Grandy, Paul R. Albert

    Research output: Contribution to journalArticle

    65 Citations (Scopus)

    Abstract

    The human dopamine D2L (long form) and D2S (short form) receptors were expressed separately in mouse Ltk- fibroblast cells to investigate whether there is a difference in transmembrane signaling of these D2 receptors. Both receptors induced two signals, a phosphatidylinositol-linked mobilization of intracellular calcium and an inhibition of cyclic adenosine 3′-5′ monophosphate (cAMP) accumulation, each with similar response magnitudes and identical pharmacology. Both calcium and cAMP signals were sensitive to pretreatment with pertussis toxin (PTX), indicating mediation by coupling to Gi/Go proteins. However, the two forms of D2 receptor were distinguished by acute prior activation of protein kinase C (PKC) with 12-O-tetradecanoyl 4β-phorbol 13-acetate (TPA): TPA blocked the D2S-mediated increase in cytosolic free calcium concentration ([Ca2+]i) in a concentration-dependent manner (between 10 nM and 1 μM), whereas the D2L receptor-induced increase in [Ca2+]i was resistant to TPA and was only partially (60%) inhibited by 100 μM TPA. By contrast, TPA did not alter the inhibition of cAMP accumulation induced by activation of either D2S or D2L receptors. We conclude that, in the L cell system, prior activation of PKC differentially modulates the transmembrane signaling of the D2L and D2S receptors, preferentially inhibiting the D2S receptor-mediated calcium signal but not altering the dopamine-induced inhibitory cAMP signal of either receptor subtype.

    Original languageEnglish (US)
    Pages (from-to)2311-2317
    Number of pages7
    JournalJournal of Neurochemistry
    Volume59
    Issue number6
    StatePublished - Dec 1992

    Fingerprint

    Adenosine
    Protein Kinase C
    Acetates
    Calcium
    Chemical activation
    Dopamine
    Calcium-Sensing Receptors
    Pertussis Toxin
    Tetradecanoylphorbol Acetate
    Phosphatidylinositols
    Fibroblasts
    Pharmacology
    Cells
    human DRD2 protein
    phorbol
    Cyclic AMP
    Proteins

    Keywords

    • Calcium
    • Cyclic AMP
    • D receptor subtypes
    • Protein kinase C
    • Transmembrane signaling

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

    Cite this

    Differential sensitivity of the short and long human dopamine D2 receptor subtypes to protein kinase C. / Liu, Ya Fang; Civelli, Olivier; Grandy, David; Albert, Paul R.

    In: Journal of Neurochemistry, Vol. 59, No. 6, 12.1992, p. 2311-2317.

    Research output: Contribution to journalArticle

    Liu, YF, Civelli, O, Grandy, D & Albert, PR 1992, 'Differential sensitivity of the short and long human dopamine D2 receptor subtypes to protein kinase C', Journal of Neurochemistry, vol. 59, no. 6, pp. 2311-2317.
    Liu, Ya Fang ; Civelli, Olivier ; Grandy, David ; Albert, Paul R. / Differential sensitivity of the short and long human dopamine D2 receptor subtypes to protein kinase C. In: Journal of Neurochemistry. 1992 ; Vol. 59, No. 6. pp. 2311-2317.
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