PMID:1331329

Citation	Liu, YF, Civelli, O, Grandy, DK and Albert, PR (1992) Differential sensitivity of the short and long human dopamine D2 receptor subtypes to protein kinase C. J. Neurochem. 59:2311-7
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 4 beta-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 microM), whereas the D2L receptor-induced increase in [Ca2+]i was resistant to TPA and was only partially (60%) inhibited by 100 microM 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.
Links	PubMed
Keywords	Adenylate Cyclase/metabolism; Animals; Calcium/analysis; Calcium/metabolism; Calcium/physiology; Cyclic AMP/metabolism; Cyclic AMP/physiology; Dopamine/pharmacology; Enzyme Activation/drug effects; Fibroblasts/chemistry; Fibroblasts/metabolism; Fibroblasts/ultrastructure; Forskolin/pharmacology; Mice; Pertussis Toxin; Protein Kinase C/pharmacology; Receptors, Dopamine D2/chemistry; Receptors, Dopamine D2/drug effects; Receptors, Dopamine D2/physiology; Signal Transduction; Tetradecanoylphorbol Acetate/pharmacology; Virulence Factors, Bordetella/pharmacology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:DRD2	involved_in	GO:0051482: positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:DRD2	involved_in	GO:0035556: intracellular signal transduction	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:DRD2	involved_in	GO:0007195: adenylate cyclase-inhibiting dopamine receptor signaling pathway	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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