BACKGROUND: G-protein receptor kinases (GRKs) are a family of serine/threonine kinases involved in the homologous desensitization of agonist activated G-protein coupled receptors (GPCRs). G-protein coupled receptor supersensitivity, possibly as a result of decreased GRK, has been suggested in affective disorders. METHODS: We used immunobloting to determine if chronic, therapeutically relevant doses of lithium (Li+), carbamazepine (CBZ), and valproate (VPA), would increase GRK2/3 protein levels in rat frontal cortex. RESULTS: Chronic Li+ (24%) and CBZ (44%) significantly increased GRK3 in the membrane but not cytosol fractions. Chronic VPA had no effect on GRK3. G-protein receptor kinase 2 protein levels were unchanged by all treatments. The GRK3 membrane to cytosol ratio was increased significantly in Li+ and CBZ treated rats. CONCLUSIONS: These results show that chronically administered Li+ and CBZ, but not VPA, increase the translocation of GRK3 from cytosol to membrane, possibly correcting supersensitivity of GPCRs in bipolar disorder.
BACKGROUND: G-protein receptor kinases (GRKs) are a family of serine/threonine kinases involved in the homologous desensitization of agonist activated G-protein coupled receptors (GPCRs). G-protein coupled receptor supersensitivity, possibly as a result of decreased GRK, has been suggested in affective disorders. METHODS: We used immunobloting to determine if chronic, therapeutically relevant doses of lithium (Li+), carbamazepine (CBZ), and valproate (VPA), would increase GRK2/3 protein levels in rat frontal cortex. RESULTS: Chronic Li+ (24%) and CBZ (44%) significantly increased GRK3 in the membrane but not cytosol fractions. Chronic VPA had no effect on GRK3. G-protein receptor kinase 2 protein levels were unchanged by all treatments. The GRK3 membrane to cytosol ratio was increased significantly in Li+ and CBZ treated rats. CONCLUSIONS: These results show that chronically administered Li+ and CBZ, but not VPA, increase the translocation of GRK3 from cytosol to membrane, possibly correcting supersensitivity of GPCRs in bipolar disorder.
Authors: Manish Taneja; Samina Salim; Kaustuv Saha; H Kevin Happe; Nidal Qutna; Frederick Petty; David B Bylund; Douglas C Eikenburg Journal: Behav Brain Res Date: 2011-02-17 Impact factor: 3.332
Authors: Michael J McCarthy; Thomas B Barrett; Stephanie Nissen; John R Kelsoe; Eric E Turner Journal: J Psychiatr Res Date: 2009-09-18 Impact factor: 4.791
Authors: Vasken L Keleshian; Matthew Kellom; Hyung-Wook Kim; Ameer Y Taha; Yewon Cheon; Miki Igarashi; Stanley I Rapoport; Jagadeesh S Rao Journal: PLoS One Date: 2014-05-05 Impact factor: 3.240