Concurrent measures of protein kinase C and phosphoinositides in lithium-treated bipolar patients and healthy individuals: a preliminary study.
This study examined the hypothesis that lithium inhibits the PI signaling pathway in humans during in vivo administration by concurrently measuring PKC isozymes and platelet membrane phosphoinositides in lithium-treated patients and healthy individuals. The platelet membrane and cytosolic levels of PKC alpha, beta I, beta II, delta, and epsilon were measured using Western blotting. The relative platelet membrane contents of phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP(2)) were measured with two-dimensional thin-layer chromatography. Nine euthymic lithium-treated bipolar subjects and 11 healthy control subjects were studied. Compared to control subjects, lithium-treated bipolar patients had significantly lower levels of cytosolic PKC alpha isozyme (t-test=-3.24, d.f.=17, P=0.01) and PIP(2) platelet membrane levels (t-test=-2.51, d.f.=18, P=0.02), and a trend toward reduced levels of cytosolic PKC beta II isozyme (t=-2.17, d.f.=17, P=0.05). There was no significant correlation between PIP(2) and any of the PKC isozymes. These preliminary findings suggest that chronic lithium treatment may decrease the levels of both cytosolic PKC alpha isozyme and membrane PIP(2) in platelets of bipolar disorder patients.
Soares
J C
JC
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.soares+@pitt.edu
Chen
G
G
Dippold
C S
CS
Wells
K F
KF
Frank
E
E
Kupfer
D J
DJ
Manji
H K
HK
Mallinger
A G
AG
D000328:Adult; D018692:Antimanic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D015153:Blotting, Western; D002450:Cell Communication / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002855:Chromatography, Thin Layer / Q000379:methods; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008094:Lithium / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010716:Phosphatidylinositols / Q000097:blood*; D011493:Protein Kinase C / Q000097:blood* / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D018692:Antimanic Agents; D010716:Phosphatidylinositols; D008094:Lithium; D011493:Protein Kinase C