Dopamine receptor signaling

J Recept Signal Transduct Res. 2004 Aug;24(3):165-205. doi: 10.1081/rrs-200029981.


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 Galphas and Galphaolf, 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 Galphai and Galphao. These pertussis toxin-sensitive G proteins regulate some effectors, such as adenylate cyclase, via their Galpha 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 Gbetagamma 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.

Publication types

  • Review

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • GTP-Binding Proteins / metabolism
  • Humans
  • Ion Channels / metabolism
  • Models, Biological
  • Receptors, Dopamine / metabolism*
  • Receptors, Glutamate / metabolism
  • Signal Transduction*
  • Type C Phospholipases / metabolism


  • Ion Channels
  • Receptors, Dopamine
  • Receptors, Glutamate
  • Cyclic AMP-Dependent Protein Kinases
  • Type C Phospholipases
  • GTP-Binding Proteins
  • Adenylyl Cyclases