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

Eldo V. Kuzhikandathil, Weifeng Yu, Gerry S. Oxford

Research output: Contribution to journalArticle

83 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)390-402
Number of pages13
JournalMolecular and Cellular Neuroscience
Volume12
Issue number6
DOIs
StatePublished - Dec 1998
Externally publishedYes

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Dopamine D3 Receptors
Inwardly Rectifying Potassium Channel
Cell Line
Somatostatin Receptors
Quinpirole
Dopamine D2 Receptors
Pertussis Toxin
Muscarinic Receptors
Barium
G-Protein-Coupled Receptors
Cricetulus
Neurotransmitter Agents
dopamine D2L receptor
Ovary
Protein Isoforms
Western Blotting
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

Human dopamine D3 and D2L receptors couple to inward rectifier potassium channels in mammalian cell lines. / Kuzhikandathil, Eldo V.; Yu, Weifeng; Oxford, Gerry S.

In: Molecular and Cellular Neuroscience, Vol. 12, No. 6, 12.1998, p. 390-402.

Research output: Contribution to journalArticle

Kuzhikandathil, Eldo V. ; Yu, Weifeng ; Oxford, Gerry S. / Human dopamine D3 and D2L receptors couple to inward rectifier potassium channels in mammalian cell lines. In: Molecular and Cellular Neuroscience. 1998 ; Vol. 12, No. 6. pp. 390-402.
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