title: Human dopamine D3 and D2L receptors couple to inward rectifier potassium channels in mammalian cell lines.
abstract: 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.
authors.affiliation: Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
authors.forename: E V
authors.initials: EV
authors.lastname: Kuzhikandathil
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.forename: G S
authors.initials: GS
authors.lastname: Oxford
mesh_terms: 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
chemical_list: 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