The Dopamine neurotransmitter belongs to catecholamines and can therefore be further converted into adrenaline and noreadrenaline. Dopamine has various physiological roles, including learning and memory, motor output and endocrine regulation. It does so by binding and activating Dopamine receptors which belong to the G-protein coupled receptor superfamily (GPCR).nThe D4 Dopamine Receptor belongs to the D2-like family as do D2 and D3 Dopamine Receptors and like all GPCRs has seven transmembrane spanning membrane regions. Structure wise members of the family share high homology in the transmembrane domains and lower homology in the extracellular N-Terminal and the intracellular C-terminal domains. Notably, the coding region of the 3rd intracellular loop of D4 Receptor is known to undergo extensive polymorphism.nLike many GPCRs, each dopamine receptor subtype can react with more than one G-protein giving rise to different signaling possibilities3. Whereas D2-like dopamine receptors are generally considered to couple to Gi, and therefore inhibit adenylyl cyclase, the signaling through D4 is complicated due to the polymorphisms in the 3rd intracellular loop. It seems that this region is important to G-coupling as different polyphormisms in the region influence the ability of D4 to couple to adenylyl cyclase and G-proteins. D4 Dopamine Receptors also influence Ca2+ levels. They could also interact with G-protein couple inwardly rectifying K+ channel to ultimately cause a decrease in the firing rate of neurons.nThe distribution of D4 Dopamine Receptor mostly includes the brain and is mainly found post-synaptically in dendritic shafts and spines of mammalian striatum.
