Table of Contents
Cardiovascular Psychiatry and Neurology
Volume 2009 (2009), Article ID 618586, 8 pages
http://dx.doi.org/10.1155/2009/618586
Research Article

Pharmacological Characterization of Inositol 1,4,5-tris Phosphate Receptors in Human Platelet Membranes

Department of Psychiatry, The Psychiatric Institute, University of Illinois at Chicago, Chicago, IL 60612, USA

Received 21 May 2009; Accepted 12 July 2009

Academic Editor: Kenji Hashimoto

Copyright © 2009 Yogesh Dwivedi and Ghanshyam N. Pandey. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The phosphatidylinositol (PI) hydrolysis signaling system has been shown to be altered in platelets of depressed and schizophrenic subjects. Inositol (1,4,5) trisphosphate (Ins(1,4,5) ), an integral component of the PI signaling system, mobilizes by activating Ins(1,4,5) receptors. To eventually investigate the role of Ins(1,4,5) receptors in depression and other mental disorders, we characterized [ ]Ins(1,4,5) binding sites in crude platelet membranes prepared from small amounts of blood obtained from healthy human control subjects. We found a single, saturable binding site for [ ]Ins(1,4,5) to crude platelet membranes, which is time dependent and modulated by pH, inositol phosphates, and heparin. Since cyclic adenosine monophosphate (cAMP) and have been shown to be important modulators in Ins(1,4,5) receptors, in the present study we also determined the effects of various concentrations of and forskolin on Ins(1,4,5) binding to platelet membranes. modulated [ ]Ins(1,4,5) binding sites in a biphasic manner: at lower concentrations it inhibited [ ]Ins(1,4,5) binding, whereas at higher concentrations, it stimulated [ ]Ins(1,4,5) binding. On the other hand, forskolin inhibited [ ]Ins(1,4,5) binding. Our results thus suggest that the pharmacological characteristics of [ ]Ins(1,4,5) binding to crude platelet membranes are similar to that of Ins(1,4,5) receptors; and that both and cAMP modulate [ ]Ins(1,4,5) binding in crude platelet membranes.