[DARPP-32 in the patients with endogenous psychosis]

Dopamine- and cyclic AMP-regulated phosphoprotein with a relative molecular weight of 32 kDa (DARPP-32) plays an important role in integrating information of about several neurotransmitters arriving at dopaminoceptive neurons. DARPP-32 is phosphorylated by dopamine D1 receptor at threonine 34 and converted to an inhibitor of protein phosphatase I. It facilitates the phosphorylation of several neurotransmitter receptors, including N-methyl-D-aspartic acid (NMDA)- and alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA)-type glutamate receptors and gamma-aminobutyric acid (GABA)A receptors. In contrast, D2 receptor stimulation induces dephosphorylation of DARPP-32, which results in dephosphorylation of the glutamate and GABAA receptors. Thus, phosphorylation and dephosphorylation of DARPP-32 regulates the functions of neurotransmitter systems. Recent studies from our laboratory and elsewhere have demonstrated that the amount of DARPP-32 in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia is lower than that in the DLPFC of control subjects. Thus, it is plausible that DARPP-32 is associated with the concurrent alterations in dopamine, glutamate, and GABA neurotransmitter systems in subjects with schizophrenia. We have also found reduced levels of DARPP-32 in the DLPFC of subjects with bipolar disorder. Thus, it is important to elucidate the role of DARPP-32 in the pathophysiology of schizophrenia and bipolar disorder.