ELEVATED [H-3]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 thi s receptor-mediated phosphatidyl inositol(PI) hydrolysis signal transd uction 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 proce sses by releasing Ca2+ from intracellular stores after binding with In s(1,4,5)P-3 receptors. To examine the role of Ins(1 4,5)P3 receptors i n depression, we determined [H-3]Ins(1,4,5)P-3 binding sites and expre ssed protein levels of Ins(1,4,5)P-3 receptors in platelets of depress ed 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 re ceptors was significantly higher in platelets of depressed subjects co mpared with normal control subjects, whereas there was no significant difference in K-D between these two groups. The immune-detectable expr essed level of Ins(1,4,5)P-3 receptor protein was also significantly i ncreased in depressed patients in contrast to the levels of normal con trol subjects. Moreover, a significant correlation was observed in B-m ax and the protein level of Ins(1,4,5)P-3 receptors. The increase in t he number of [H-3]Ins(1,4,5)P-3 binding sites in platelets of depresse d 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 recep tors receptors may be involved in the pathophysiology of depression.