Journal article
Lithium and valproic acid treatments reduce PKC activation and receptor-G protein coupling in platelets of bipolar manic patients
Journal of psychiatric research, v 39(4), pp 355-363
01 Jul 2005
PMID: 16044535
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 μM 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]GTPγS binding to membrane Gα 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]GTPγS binding to Gα proteins was detected in BD manic but not in schizophrenic patients although basal [35S]GTPγS 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.
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Details
- Title
- Lithium and valproic acid treatments reduce PKC activation and receptor-G protein coupling in platelets of bipolar manic patients
- Creators
- Chang-Gyu Hahn - Medical College of Pennsylvania, Philadelphia, PA, USAUmapathy - Western Pennsylvania Psychiatric Institute, Pittsburg, PA, USAHoau-Yan Wang - City College of New YorkRamesh Koneru - Medical College of Pennsylvania, Philadelphia, PA, USADouglas F. Levinson - Medical College of Pennsylvania, Philadelphia, PA, USAEitan Friedman - City College of New York
- Publication Details
- Journal of psychiatric research, v 39(4), pp 355-363
- Publisher
- Elsevier
- Number of pages
- 9
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000230295900003
- Scopus ID
- 2-s2.0-15544363025
- Other Identifier
- 991020668907704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Psychiatry