Altered 5-HT-induced calcium response in the presence of staurosporine in blood platelets from bipolar disorder patients.
We have reported that the platelet intracellular calcium (Ca) mobilization after stimulation by serotonin (5-HT) is specifically enhanced in bipolar disorder among various psychiatric disorders, compared with that in normal control. To explore the mechanisms of enhanced Ca response to 5-HT in the platelets, we first examined the relation between the 5HT-elicited Ca mobilization and 5-HT(2A) receptor density using the platelets from 13 normal subjects. From this study, we found no significant correlation between two measures. Then, we investigated the effects of staurosporine, a protein kinase C (PKC) inhibitor, on Ca response to 5-HT in platelets from patients with major depressive disorder (unipolar), bipolar disorder, and normal controls. While 5-HT-induced Ca mobilization, in the presence of 100 nM staurosporine, was significantly attenuated in normal controls and patients with major depressive disorder, the inhibitory effect of staurosporine was not observed in bipolar disorder. These results suggest that the failure in inhibiting the platelet intracellular Ca response to 5-HT in bipolar disorder may be related to increased activity of PKC rather than increased 5-HT(2A) receptor number. Moreover, the trend of the Ca response towards staurosporine may become a specific biological marker for unipolar-bipolar dichotomy.
Suzuki
Katsuji
K
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Japan. kasuzuki@med.hokudai.ac.jp
Kusumi
Ichiro
I
Akimoto
Tatsuyuki
T
Sasaki
Yuki
Y
Koyama
Tsukasa
T
D000328:Adult; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000097:blood* / Q000201:enzymology; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D019311:Staurosporine / Q000494:pharmacology*
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012701:Serotonin; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium