Decreased GRK3 but not GRK2 expression in frontal cortex from bipolar disorder patients.
Overactivation of G-protein-mediated functions and altered G-protein regulation have been reported in bipolar disorder (BD) brain. Further, drugs effective in treating BD are reported to up-regulate expression of G-protein receptor kinase (GRK) 3 in rat frontal cortex. We therefore hypothesized that some G-protein subunits and GRK levels would be reduced in the brain of BD patients. We determined protein and mRNA levels of G-protein beta and gamma subunits, GRK2, and GRK3 in post-mortem frontal cortex from 10 BD patients and 10 age-matched controls by using immunoblots and real-time RT-PCR. There were statistically significant decreases in protein and mRNA levels of G-protein subunits beta and gamma and of GRK3 in BD brain but not a significant difference in the GRK2 level. Decreased expression of G-protein subunits and of GRK3 may alter neurotransmission, leading to disturbed cognition and behaviour in BD.
Rao
Jagadeesh S
JS
Brain Physiology and Metabolism Section, NIA, NIH, Bethesda, MD 20892, USA. jrao@grc.nia.nih.gov
Rapoport
Stanley I
SI
Kim
Hyung-Wook
HW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001714:Bipolar Disorder / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism*; D054770:G-Protein-Coupled Receptor Kinase 3 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism; D013223:Statistics as Topic
D012333:RNA, Messenger; D054770:G-Protein-Coupled Receptor Kinase 3; C496567:GRK2 protein, human; C517848:GRK3 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2