Five subtypes of dopamine receptors exist in two subfamilies: two D1-like (D1 and D5) and three D2-like (D2, D3 and D4). As members of the G protein-coupled receptor (GPCR) family, dopamine receptors initiate their biological function by coupling to GTP regulatory proteins (G proteins). D1-like receptors, DRD1 and DRD5, stimulate adenylyl cyclase whereas D2-like receptors, DRD2, DRD3 and DRD4, are coupled to inhibitory G proteins and their stimulation leads to the inhibition of adenylyl cyclase activity, and subsequent respective cellular signaling. All five subtypes have seven transmembrane domains, an extracellular amino terminus, and an intracellular carboxyl terminus. Allelic variants of the D4 dopamine receptor (DRD4) are known characterized risk factors of ADHD. It is reported that hypoxia enhances DRD4 promoter activity by several fold. It is also thought that dopamine receptors such as DRD4 are involved in neuroexcitation and in a variety of other neurological and psychiatric disorders.
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