Possible involvement of post-dopamine D2 receptor signalling components in the pathophysiology of schizophrenia

Abstract

Par-4 has been suggested to mediate dopamine neurotransmission. Dopamine D2 receptor (DRD2) activation induces a signalling complex of AKT1, PP2A and β-arrestin2 which dephosphorylates/inactivates AKT1 thereby activating GSK-3β, transducing dopamine-dependent behaviour. DRD2 activation also results in down-regulation of PKA activity. Among other substrates PKA phosphorylates GSK-3β. Prolonged DRD2 activation leads to its 'desensitization' which involves GRKs and β-arrestins. β-arrestin1 binds to phosphorylated receptors preventing further G-protein stimulation. This study examined whether Par-4, β-arrestin1, AKT1 and GSK-3β are involved in the pathophysiology of schizophrenia. Lymphocytes ob..