[Serotonin-2 receptor-mediated intraplatelet calcium mobilization in affective disorders: relevance to the pathophysiology of depression]

Abstract

Abnormal serotonin-2(5-HT2) receptor function in the central nervous system has been suggested to play a role in the pathogenesis of affective disorders. The presence of 5-HT2 receptors on human platelet similar to those in brain may permit direct study of 5-HT2 receptor function in living persons. 5-HT-stimulated intracellular calcium (Ca) concentration change was studied in the platelets of healthy subjects, using fluorescent Ca indicator fura-2. 5-HT increased the Ca response in a concentration-dependent manner. The maximal response was obtained at 10 microM of 5-HT and its EC50 value was 0.4 microM. This response was potently inhibited by selective 5-HT2 receptor antagonists, suggesting that the 5-HT-induced Ca mobilization is mediated by 5-HT2 receptors. This 5-HT-stimulated Ca response was not significantly affected by the time of blood sampling, gender, age, meal or exercise. Therefore, it may be concluded that the 5-HT-induced Ca response in human platelets is a stable parameter and that it is suitable for assessing 5-HT2 receptor function in depressed patients. Thus, the 5-HT-induced Ca mobilization was measured in the platelets of depressed patients. The response was significantly higher in unmedicated patients with bipolar depression and melancholic major depression than in those with non-melancholic major depression and normal controls. The enhanced Ca response to 5-HT failed to correlate with severity of depressive symptoms. In patients with bipolar depression and melancholic major depression, there was no significant difference in 5-HT-stimulated Ca response between unmediated group and euthymic-treated group. These results suggest that 5-HT2 receptor function is increased in some type of affective disorders and that the enhanced Ca response to 5-HT may be trait dependent rather than state dependent.