Chronic treatment with mood stabilizers increases membrane GRK3 in rat frontal cortex.
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.
Ertley
Renee N
RN
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Bazinet
Richard P
RP
Lee
Ho-Joo
HJ
Rapoport
Stanley I
SI
Rao
Jagadeesh S
JS
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*
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