Elevated [3H]inositol 1,4,5 trisphosphate binding sites and expressed inositol 1,4,5 trisphosphate receptor protein level in platelets of depressed patients

Several reports suggest that serotonin(2A) (5HT(2A)) receptors and this receptor-mediated phosphatidyl inositol(PI) hydrolysis signal transduction system are altered in platelets of depressed patients. Inositol 1,4,5-trisphosphate (Ins[1,4,5]P-3), an important component of the PI signaling system, plays a crucial role in various physiological processes by releasing Ca2+ from intracellular stores after binding with Ins(1,4,5)P-3 receptors. To examine the role of Ins(1 4,5)P3 receptors in depression, we determined [H-3]Ins(1,4,5)P-3 binding sites and expressed protein levels of Ins(1,4,5)P-3 receptors in platelets of depressed patients (n = 15) and normal control subjects (n = 17). We observed that the mean B-max of [H-3]Ins(1,4,5)P-3 binding to Ins(1,4,5)P-3 receptors was significantly higher in platelets of depressed subjects compared with normal control subjects, whereas there was no significant difference in K-D between these two groups. The immune-detectable expressed level of Ins(1,4,5)P-3 receptor protein was also significantly increased in depressed patients in contrast to the levels of normal control subjects. Moreover, a significant correlation was observed in B-max and the protein level of Ins(1,4,5)P-3 receptors. The increase in the number of [H-3]Ins(1,4,5)P-3 binding sites in platelets of depressed subjects appears to be due to an increase in the amount of Ins(1,4,5)P-3 receptor proteins. These results suggest that Ins(1,4,5)P-3 receptors receptors may be involved in the pathophysiology of depression.