Altered 5-HT-induced calcium response in the presence of staurosporine in blood platelets from bipolar disorderpatients

Abstract

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 Caresponse to 5-HT in the platelets, we first examined the relation between the 5HT-elicited Ca mobilization and 5-HT2A receptor densityusing the platelets from 13 normalsubjects. From this study, we found no significant correlation between two measures. Then, weinvestigated the effects of staurosporine, a protein kinase C (PKC) inhibitor, on Ca response to 5-HT in platelets from patients with majordepressive disorder (unipolar), bipolar disorder, and normalcontrols. While 5-HT-induced Ca mobilization, in the presence of 100 nMstaurosporine, was significantly attenuated in normalcontrols and patients with major depressive disorder, the inhibitory effect ofstaurosporine was not observed in bipolar disorder. These results suggest that the failure in inhibiting the platelet intracellular Caresponse to 5-HT in bipolar disorder may be related to increased activity of PKC rather than increased 5-HT2Areceptor number.Moreover, the trend of the Ca response towards staurosporine may become a specific biologicalmarker for unipolar-bipolar dichotomy. © 2003 Nature Publishing Group.