Human dopamine D3 and D2L receptors couple to inward rectifier potassium channels in mammalian cell lines

Mol Cell Neurosci. 1998 Dec;12(6):390-402. doi: 10.1006/mcne.1998.0722.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • CHO Cells / chemistry*
  • Cricetinae
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / pharmacology
  • Electrophysiology
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Gene Expression / physiology
  • Humans
  • Mammals
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Pertussis Toxin
  • Pituitary Gland / cytology
  • Potassium / metabolism
  • Potassium Channels / agonists
  • Potassium Channels / analysis
  • Potassium Channels / genetics*
  • Potassium Channels, Inwardly Rectifying*
  • Quinpirole / pharmacology
  • Receptors, Dopamine D2 / analysis
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D3
  • Receptors, Somatostatin / analysis
  • Receptors, Somatostatin / genetics
  • Sodium Chloride / pharmacology
  • Somatostatin / pharmacology
  • Spiperone / pharmacology
  • Transfection
  • Tritium
  • Virulence Factors, Bordetella / pharmacology


  • DRD3 protein, human
  • Dopamine Agonists
  • Dopamine Antagonists
  • Drd3 protein, mouse
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Kcnj3 protein, mouse
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Receptors, Somatostatin
  • Virulence Factors, Bordetella
  • Tritium
  • Quinpirole
  • Sodium Chloride
  • Spiperone
  • Somatostatin
  • Adenosine Triphosphate
  • Pertussis Toxin
  • Potassium