Dopaminergic signaling pathways, which are essential for multiple brain functions, are abnormal in several neurological disorders, such as schizophrenia, Parkinson's disease and drug abuse. DARPP-32 (for dopamine and adenosine 3',5'-monophosphate-regulated phosphoprotein) is abundant in neurons that receive dopaminergic input. Activation of PKA and the consequent phosphorylation of DARPP-32 on threonine occurs in response to dopamine acting upon D1-like receptors. Dopamine interaction with D2-like receptors results in the inhibition of PKA activation, the activation of protein phosphatase 2B and the consequent dephosphorylation of DARPP-32. Neurotransmitters other than dopamine may also be able to stimulate the phosphorylation or dephosphorylation of DARPP-32. Phosphorylated DARPP-32 is a potent inhibitor of PP-1.
