Human dopamine D3 and D2L receptors couple to inward rectifier potassium channels in mammalian cell lines.
The molecular mechanisms coupling the D3 dopamine receptor to downstream effectors have neither been well defined nor well characterized. Here we examine the coupling of the human D3 receptor to G-protein coupled inward rectifier potassium channels (GIRKs) in mammalian cells. Human D3 receptors couple strongly to homomeric human GIRK2 channels coexpressed in Chinese hamster ovary (CHO) cells, with a coupling efficiency comparable to that of D2L receptors. The coupling between D3 receptors and native GIRK channels was examined in an AtT-20 mouse pituitary cell line stably expressing the human D3 receptor. AtT-20 cells endogenously express somatostatin and muscarinic receptors coupled to GIRK channels. RT-PCR and Western blot analyses revealed that AtT-20 cells natively express Kir3.1 and Kir3.2 channel isoforms, but not D2 or D3 dopamine receptors. In D3 receptor expressing AtT-20 cells, application of the D2/D3 receptor agonist, quinpirole, induces pertussis toxin-sensitive inward rectifying K+ currents that are blocked by barium. Activation of D3 receptors leads to both homologous desensitization of this receptor and an unusual unidirectional heterologous desensitization of somatostatin receptors. AtT-20 cells may be a good model to examine the functional role of D3 dopamine receptors in regulating neurotransmitter secretion.
Kuzhikandathil
E V
EV
Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
Yu
W
W
Oxford
G S
GS
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells / Q000737:chemistry*; D006224:Cricetinae; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004594:Electrophysiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008322:Mammals; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D037342:Pertussis Toxin; D010902:Pituitary Gland / Q000166:cytology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000819:agonists / Q000032:analysis / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000235:genetics*; D050637:Receptors, Dopamine D3; D017481:Receptors, Somatostatin / Q000032:analysis / Q000235:genetics; D012965:Sodium Chloride / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D014162:Transfection; D014316:Tritium; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C493593:DRD3 protein, human; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C493594:Drd3 protein, mouse; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497067:Kcnj3 protein, mouse; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D017481:Receptors, Somatostatin; D010566:Virulence Factors, Bordetella; D014316:Tritium; D019257:Quinpirole; D012965:Sodium Chloride; D013134:Spiperone; D013004:Somatostatin; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D011188:Potassium