Dopamine receptor signaling

Kim A. Neve, Jeremy K. Seamans, Heather Trantham-Davidson

Research output: Contribution to journalArticlepeer-review

649 Scopus citations


The D1-like (D1, D5) and D2-like (D2, D3, D4) classes of dopamine receptors each has shared signaling properties that contribute to the definition of the receptor class, although some differences among subtypes within a class have been identified. D1-like receptor signaling is mediated chiefly by the heterotrimeric G proteins Gαs and Gαolf, which cause sequential activation of adenylate cyclase, cylic AMP-dependent protein kinase, and the protein phosphatase-1 inhibitor DARPP-32. The increased phosphorylation that results from the combined effects of activating cyclic AMP-dependent protein kinase and inhibiting protein phosphatase 1 regulates the activity of many receptors, enzymes, ion channels, and transcription factors. D1 or a novel D1-like receptor also signals via phospholipase C-dependent and cyclic AMP-independent mobilization of intracellular calcium. D2-like receptor signaling is mediated by the heterotrimeric G proteins Gαi and Gαo. These pertussis toxin-sensitive G proteins regulate some effectors, such as adenylate cyclase, via their Gα subunits, but regulate many more effectors such as ion channels, phospholipases, protein kinases, and receptor tyrosine kinases as a result of the receptor-induced liberation of Gβγ subunits. In addition to interactions between dopamine receptors and G proteins, other protein:protein interactions such as receptor oligomerization or receptor interactions with scaffolding and signal-switching proteins are critical for regulation of dopamine receptor signaling.

Original languageEnglish (US)
Pages (from-to)165-205
Number of pages41
JournalJournal of Receptors and Signal Transduction
Issue number3
StatePublished - 2004


  • Adenylate cyclase
  • Calcium channel
  • Extracellular signal-regulated kinase
  • G protein
  • Glutamate
  • Phospholipase
  • Potassium channel
  • Protein kinase
  • Sodium channel

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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