Recent studies suggest that cells respond to many stimuli, which act at the cell surface, by hydrolysis of phosphatidyl inositol bisphosphate to release inositol trisphosphate into the cytoplasm where it binds to the endoplasmic reticulum and leads to the mobilization of bound Ca++ that, in turn, modulates the activity of many enzymes and cellular processes. This model of inositol trisphosphate acting as a second messenger leads to the postulate that a specific receptor resides on the surface of the endoplasmic reticulum to which the messenger binds and causes internal Ca++ to escape into the cytoplasm. It is the aim of this proposal to demonstrate the existence of such a receptor, to isolate it, and to study its properties. The demonstration of the receptor will be based on binding studies using a tritium-labeled analog of myoinositol trisphosphate, and the isolation of the receptor will make use of an immobilized myoinositol trisphosphate analog that can be employed in affinity chromatography of the detergent-solubilized receptor. Once purified, the receptor will be studied to determine its composition, subunit organization, and binding specificity for different phosphate analogs of the natural ligand. This research should lead to a better understanding of the biochemistry of cell growth regulation.