title: Chronic treatment with mood stabilizers increases membrane GRK3 in rat frontal cortex.
abstract: 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.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Renee N
authors.initials: RN
authors.lastname: Ertley
authors.forename: Richard P
authors.initials: RP
authors.lastname: Bazinet
authors.forename: Ho-Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
authors.forename: Jagadeesh S
authors.initials: JS
authors.lastname: Rao
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D018692:Antimanic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002220:Carbamazepine / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects*; D054769:G-Protein-Coupled Receptor Kinase 2; D054770:G-Protein-Coupled Receptor Kinase 3; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013570:Synaptic Membranes / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology*; D051552:beta-Adrenergic Receptor Kinases / Q000378:metabolism*
chemical_list: D000927:Anticonvulsants; D018692:Antimanic Agents; D002220:Carbamazepine; D014635:Valproic Acid; D054770:G-Protein-Coupled Receptor Kinase 3; C496569:Grk2 protein, rat; C517851:Grk3 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2; D018021:Lithium Chloride