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

Abstract

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]P₃), 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)P₃ receptors. To examine the role of Ins(1,4,5)P₃ receptors in depression, we determined [³H]Ins(1,4,5)P₃ binding sites and expressed protein levels of Ins(1,4,5)P₃ receptors in platelets of depressed patients (n = 15) and normal control subjects (n = 17). We observed that the mean B_max of [³H]Ins(1,4,5)P₃ binding to Ins(1,4,5)P₃ 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 immuno-detectable expressed level of Ins(1,4,5)P₃ 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)P₃ receptors. The increase in the number of [³H]Ins(1,4,5)P₃ binding sites in platelets of depressed subjects appears to be due to an increase in the amount of Ins(1,4,5)P₃ receptor proteins. These results suggest that Ins(1,4,5)P₃ receptors may be involved in the pathophysiology of depression.