Dopamine receptors - IUPHAR Review 13

Abstract

The variety of physiological functions controlled by dopamine in the brain and periphery is mediated by the D1, D2, D3, D4 and D5 dopamine GPCRs. Drugs acting on dopamine receptors are significant tools for the management of several neuropsychiatric disorders including schizophrenia, bipolar disorder, depression and Parkinson's disease. Recent investigations of dopamine receptor signalling have shown that dopamine receptors, apart from their canonical action on cAMP-mediated signalling, can regulate a myriad of cellular responses to fine-tune the expression of dopamine-associated behaviours and functions. Such signalling mechanisms may involve alternate G protein coupling or non-G protein mechanisms involving ion channels, receptor tyrosine kinases or proteins such as β-arrestins that are classically involved in GPCR desensitization. Another level of complexity is the growing appreciation of the physiological roles played by dopamine receptor heteromers. Applications of new in vivo techniques have significantly furthered the understanding of the physiological functions played by dopamine receptors. Here we provide an update of the current knowledge regarding the complex biology, signalling, physiology and pharmacology of dopamine receptors.

Figure 1

Schematic diagram representing the signalling cascades activated by the D₁ dopamine receptor (D1R). D5R, D₅ dopamine receptor; D1R:D2R, D₁–D₂ receptor heteromer.

Figure 2

Schematic diagram representing the signalling cascades activated by the D₂ dopamine receptor (D2R). BMAL1, aryl hydrocarbon receptor nuclear translocator-like protein; Clock, circadian locomotor output cycles kaput gene; Cry2, cryptochrome 2; KLC2, kinesin light chain 2; Rev/Erbα, nuclear receptor subfamily 1, group D, member 1.

Figure 3

Mechanisms and signalling events involved in the transactivation of RTK by dopamine receptors. Raf, proto-oncogene serine/threonine-PK; Ras, rat sarcoma family of small GTPases.