Dopamine receptor signaling.
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.
Neve
Kim A
KA
Veterans Affairs Medical Center and Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon, USA. nevek@ohsu.edu
Seamans
Jeremy K
JK
Trantham-Davidson
Heather
H
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D008954:Models, Biological; D011954:Receptors, Dopamine / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D007473:Ion Channels; D011954:Receptors, Dopamine; D017470:Receptors, Glutamate; D017868:Cyclic AMP-Dependent Protein Kinases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases