Expression of dopamine D2 receptor in PC-12 cells and regulation of membrane conductances by dopamine.
PC-12 cells depolarize during hypoxia and release dopamine. The hypoxia-induced depolarization is due to inhibition of an O2-sensitive K+ current. The role of dopamine released during hypoxia is uncertain, but it could act as an autocrine to modulate membrane conductance during hypoxia. The current study was undertaken to investigate this possibility. Reverse transcription-polymerase chain reaction and sequence analysis revealed that the D2 isoform of the dopamine receptor is expressed in rat PC-12 cells. Exogenously applied dopamine and the D2 agonist quinpirole elicited inhibition of a voltage-dependent K+ current (I(K)) that was prevented by sulpiride, a D2 receptor antagonist. Dopamine and quinpirole applied during hypoxia potentiated the inhibitory effect of hypoxia on I(K). We also found that quinpirole caused reversible inhibition of a voltage-dependent Ca2+ current (I(Ca)) and attenuation of the increase in intracellular free Ca2+ during hypoxia. Our results indicate that dopamine released from PC-12 cells during hypoxia acts via a D2 receptor to "autoregulate" I(K) and I(Ca).
Zhu
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WH
Department of Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, Ohio 45267-0576, USA.
Conforti
L
L
Millhorn
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DE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D004553:Electric Conductivity; D006706:Homeostasis; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D016716:PC12 Cells; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis*; D013469:Sulpiride / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D015221:Potassium Channels; D017448:Receptors, Dopamine D2; D010566:Virulence Factors, Bordetella; D019257:Quinpirole; D013469:Sulpiride; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002118:Calcium; D004298:Dopamine