Differential Sensitivity of the Short and Long Human Dopamine D2 Receptor Subtypes to Protein Kinase C

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

    Research output: Contribution to journalArticlepeer-review

    66 Scopus citations

    Abstract

    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
    DOIs
    StatePublished - Dec 1992

    Keywords

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

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

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