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Differential Sensitivity of the Short and Long Human Dopamine D 2 Receptor Subtypes to Protein Kinase C
Author(s) -
Liu Ya Fang,
Civelli Olivier,
Grandy David K.,
Albert Paul R.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb10125.x
Subject(s) - receptor , protein kinase c , pertussis toxin , g protein , dopamine receptor , signal transduction , biology , second messenger system , phospholipase c , microbiology and biotechnology , endocrinology , medicine , biochemistry
The human dopamine D 2L (long form) and D 2S (short form) receptors were expressed separately in mouse Ltk − fibroblast cells to investigate whether there is a difference in transmembrane signaling of these D 2 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 G i /G o proteins. However, the two forms of D 2 receptor were distinguished by acute prior activation of protein kinase C (PKC) with 12‐ O ‐tetradecanoyl 4β‐phorbol 13‐acetate (TPA): TPA blocked the D 2S ‐mediated increase in cytosolic free calcium concentration ([Ca 2+ ] i ) in a concentration‐dependent manner (between 10 n M and 1 μ M ), whereas the D 2L receptor‐induced increase in [Ca 2+ ] i was resistant to TPA and was only partially (60%) inhibited by 100 μ M TPA. By contrast, TPA did not alter the inhibition of cAMP accumulation induced by activation of either D 2S or D 2L receptors. We conclude that, in the L cell system, prior activation of PKC differentially modulates the transmembrane signaling of the D 2L and D 2S receptors, preferentially inhibiting the D 2S receptor‐mediated calcium signal but not altering the dopamine‐induced inhibitory cAMP signal of either receptor subtype.