A flow-cytometric method to investigate glutamate-receptor-sensitivity in whole blood platelets - results from healthy controls and patients with schizophrenia.
Hypofunction of glutamate receptors may contribute to the symptoms of schizophrenia. Human platelets express glutamate receptors and can serve as peripheral surrogate model for neuronal cells. Aim of this study was to establish a fast and sensitive flow-cytometric method to determine the glutamate-dependent kinetics of intracellular calcium ([Ca++]i) mobilization in platelets of schizophrenic patients. Glutamate stimulated [Ca++]i response was measured with a flow-cytometer in anti-CD-41a-labelled whole blood platelets of treated schizophrenic patients (n=18) and controls (n=18). In two control experiments the NMDA-receptor antagonist MK-801 and the dopamine antagonist amisulpride, respectively, were added to probes from healthy subjects. Stimulation with glutamate led dose-dependently to a mobilization of [Ca++]i in both healthy controls and patients. This effect was significantly reduced in patients. In vitro NMDA-antagonism inhibited the glutamate response, whereas dopamine-antagonism had no effect. Our flow-cytometric method allows to measure glutamate-receptor mediated [Ca++]i response in whole blood platelets, without requiring platelet rich preparations. The reduced glutamate-response in the patients was not explained by a direct inhibitory treatment effect. However, further studies with drug naive patients will be necessary to find out whether or not the observed hypoglutamergic function of platelets is endogenous to the disorder.
Baier
Paul C
PC
Department of Psychiatry and Psychotherapy, Christian-Albrechts-University Kiel, Niemannsweg 147, 24105 Kiel, Germany. p.baier@zip-kiel.de
Koch
Jakob M
JM
Seeck-Hirschner
Mareen
M
Ohlmeyer
Kathrin
K
Wilms
Sibylle
S
Aldenhoff
Josef B
JB
Hinze-Selch
Dunja
D
D000328:Adult; D000077582:Amisulpride; D000704:Analysis of Variance; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D016291:Dizocilpine Maleate / Q000097:blood; D018492:Dopamine Antagonists / Q000097:blood; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000097:blood; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017470:Receptors, Glutamate / Q000097:blood*; D012016:Reference Values; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000097:blood*; D012680:Sensitivity and Specificity; D013469:Sulpiride / Q000031:analogs & derivatives / Q000097:blood; D055815:Young Adult
D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D016291:Dizocilpine Maleate; D013469:Sulpiride; D000077582:Amisulpride; D002118:Calcium