Dopamine Receptor Signaling

Dopamine is a neurotransmitter that is important to vital brain functions like motor control and short term memory. Guanosine triphosphate cyclohydrolase I (GCH1) catalyzes the production of tetrahydrobiopterin (BH4), a required cofactor for tyrosine hydroxylase (TH), which is the rate-limiting enzyme in dopamine biosynthesis. TH is required for the conversion of L-tyrosine to L-DOPA which is then converted to dopamine. Dopamine is released at the synapse of the presynaptic neuron where it binds to its receptor on the postsynaptic neuron.Dopamine receptors are G-protein coupled receptors that can belong to either of two subtypes: D1-like receptor (D1, D5) or D2-like receptor (D2, D3, D4). D2-like receptors are coupled to Gαi which inhibits adenyl cyclase. D1 type receptors are coupled to Gαs which results in sequential activation of adenyl 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 the protein phosphatase, regulates the activity of many receptors, enzymes, ion channels, and transcription factors which mediate dopamine action.Dopamine is targeted for inactivation by its uptake via dopamine transporter (DAT). It is then enzymatically degraded by catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO) to homovanillic acid which enters the cerebrospinal fluid.