title: Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder.
abstract: Alterations of multiple G protein-mediated signaling pathways are detected in schizophrenia. G protein-coupled receptor kinases (GRKs) and arrestins terminate signaling by G protein-coupled receptors exerting a powerful influence on receptor functions. Modifications of arrestin and/or GRKs expression may contribute to schizophrenia pathology. Cortical expression of arrestins and GRKs was measured postmortem in control and subjects with schizophrenia or schizoaffective disorder. Additionally, arrestin/GRK expression was determined in elderly patients with schizophrenia and age-matched control. Patients with schizophrenia, but not schizoaffective disorder, displayed a reduced concentration of arrestin and GRK mRNAs and GRK3 protein. Arrestins and GRK significantly decreased with age. In elderly patients, GRK6 was reduced, with other GRKs and arrestins unchanged. A reduced cortical concentration of GRKs in schizophrenia (resembling that in aging) may result in altered G protein-dependent signaling, thus contributing to prefrontal deficits in schizophrenia. The data suggest distinct molecular mechanisms underlying schizophrenia and schizoaffective disorder.
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Bychkov
authors.forename: M R
authors.initials: MR
authors.lastname: Ahmed
authors.forename: V V
authors.initials: VV
authors.lastname: Gurevich
authors.forename: J L
authors.initials: JL
authors.lastname: Benovic
authors.forename: E V
authors.initials: EV
authors.lastname: Gurevich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019390:Arrestins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D054770:G-Protein-Coupled Receptor Kinase 3 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D054768:G-Protein-Coupled Receptor Kinases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D011618:Psychotic Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult
chemical_list: D019390:Arrestins; D054770:G-Protein-Coupled Receptor Kinase 3; C496567:GRK2 protein, human; C517848:GRK3 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2; D054774:G-Protein-Coupled Receptor Kinase 5; D054768:G-Protein-Coupled Receptor Kinases; C089176:G-protein-coupled receptor kinase 6; C517898:GRK5 protein, human