PMID- 16044535
OWN - NLM
STAT- MEDLINE
DCOM- 20051014
LR  - 20190922
IS  - 0022-3956 (Print)
IS  - 0022-3956 (Linking)
VI  - 39
IP  - 4
DP  - 2005 Jul
TI  - Lithium and valproic acid treatments reduce PKC activation and receptor-G protein 
      coupling in platelets of bipolar manic patients.
PG  - 355-63
AB  - Dysregulated protein kinase C (PKC) distribution and activation, and abnormal 
      receptor-G protein coupling, have been implicated in the pathophysiology of 
      bipolar affective disorder (BD). The therapeutic effectiveness of lithium has 
      also been correlated with its ability to reduce PKC activation and G 
      protein-mediated signaling. We examine the cellular distribution and activation 
      of PKC and receptor-G protein coupling in blood platelets from normal controls, 
      patients with BD mania or schizophrenia during treatment-free state, and after 
      lithium or valproic acid administration. PKC activity was measured under basal 
      and 50 nM phorbol 12-myristate, 13-acetate (PMA), 1 microM serotonin or 0.5 U/ml 
      thrombin-stimulated conditions. The coupling of G proteins to serotonin or 
      thrombin receptors were assessed by serotonin or thrombin-mediated [35S]GTPgammaS 
      binding to membrane Galpha proteins. The results demonstrate that 
      membrane-associated PKC activity and stimulus-induced PKC translocation are 
      increased in BD manic, whereas stimulus-elicited PKC translocation is attenuated 
      in schizophrenic patients. Lithium and valproic acid treatments attenuated the 
      stimulus-induced PKC translocations to a similar degree and decreased PKC 
      activity in both cytosolic and membranous fractions after two weeks of drug 
      administration. An increase in 5-HT or thrombin stimulated [35S]GTPgammaS binding 
      to Galpha proteins was detected in BD manic but not in schizophrenic patients 
      although basal [35S]GTPgammaS binding was not different across the diagnostic 
      groups. Lithium and valproic acid treatments similarly reduced receptor-G protein 
      coupling with comparable time courses. Thus, increased membrane-associated PKC, 
      cytosol to membrane PKC translocation and receptor-G protein coupling in 
      platelets of BD manic patients were alleviated by lithium or valproic acid 
      treatments.
FAU - Hahn, Chang-Gyu
AU  - Hahn CG
AD  - Medical College of Pennsylvania, Philadelphia, PA, USA.
FAU - Umapathy
AU  - Umapathy
FAU - Wang, Hoau-Yan
AU  - Wang HY
FAU - Koneru, Ramesh
AU  - Koneru R
FAU - Levinson, Douglas F
AU  - Levinson DF
FAU - Friedman, Eitan
AU  - Friedman E
LA  - eng
GR  - MH60964/MH/NIMH NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Psychiatr Res
JT  - Journal of psychiatric research
JID - 0376331
RN  - 0 (Antimanic Agents)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - G4962QA067 (Lithium Chloride)
SB  - IM
MH  - Adult
MH  - Antimanic Agents/*pharmacology/*therapeutic use
MH  - Bipolar Disorder/*drug therapy/*physiopathology
MH  - Blood Platelets/physiology
MH  - Enzyme Activation
MH  - Female
MH  - GTP-Binding Proteins/*physiology
MH  - Humans
MH  - Lithium Chloride/*pharmacology/*therapeutic use
MH  - Male
MH  - Protein Kinase C/*metabolism
MH  - Schizophrenia/*drug therapy/*physiopathology
MH  - Signal Transduction
MH  - Valproic Acid/*pharmacology/*therapeutic use
EDAT- 2005/07/27 09:00
MHDA- 2005/10/15 09:00
CRDT- 2005/07/27 09:00
PHST- 2005/07/27 09:00 [pubmed]
PHST- 2005/10/15 09:00 [medline]
PHST- 2005/07/27 09:00 [entrez]
AID - 10.1016/j.jpsychires.2004.10.007 [doi]
PST - ppublish
SO  - J Psychiatr Res. 2005 Jul;39(4):355-63. doi: 10.1016/j.jpsychires.2004.10.007.