Increased sensitivity to agonist stimulation of the Ca2+ response in neutrophils of manic-depressive patients: effect of lithium therapy.
The agonist-stimulated increase of intracellular free-Ca2+ concentration, an indicator of the sensitivity of the inositol phospholipid second-messenger generating system, was measured in neutrophils from patients with manic-depressive disorder, and controls. Dose-response curves of the calcium response were determined by measuring the fluorescence of neutrophils loaded with fura-2 and stimulated with various concentrations of the chemotactic tripeptide formylmethionylleucylphenylalanine. EC50 values were obtained for 14 medication-free patients (5 acutely depressive, and 9 symptom free remitted patients with a history of manic-depression or recurrent major depression), 9 lithium-treated, euthymic manic-depressive patients and 10 drug-free healthy controls. The EC50 values of the untreated patients were significantly lower than in the controls. Lithium-treated patients had EC50 values significantly higher than controls. These results suggest that manic-depressive disorder is associated with an increased sensitivity of the inositol phospholipid second-messenger generating system, which is counteracted by lithium treatment.
van Calker
D
D
Department of Psychiatry, University of Freiburg, FRG.
Förstner
U
U
Bohus
M
M
Gebicke-Härter
P
P
Hecht
H
H
Wark
H J
HJ
Berger
M
M
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000378:metabolism* / Q000523:psychology; D002118:Calcium / Q000378:metabolism*; D005260:Female; D016257:Fura-2; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D008094:Lithium / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D007295:Inositol Phosphates; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008094:Lithium; D002118:Calcium; D016257:Fura-2