Inositol 1,4,5-trisphosphate releases Ca2+ from a Ca2+-transporting membrane vesicle fraction derived from human platelets

• Published in: The Journal of biological chemistry 1985-01, Vol.260 (2), p.956-962
• Main Authors: ÓROURKE, F. A, HALENDA, S. P, ZAVOICO, G. B, FEINSTEIN, M. B
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - ultrastructure; Calcimycin - pharmacology; Calcium - metabolism; Cell physiology; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Humans; Inositol 1,4,5-Trisphosphate; Inositol Phosphates - pharmacology; Membrane and intracellular transports; Membranes - metabolism; Molecular and cellular biology; NADPH-Ferrihemoprotein Reductase - metabolism; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols - metabolism; Sugar Phosphates - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(20)71193-2

Human platelet membrane vesicles that accumulated Ca2+ in the presence of ATP were isolated on an isoosmotic KCl-Percoll gradient. ATP-dependent Ca2+ uptake was stimulated by oxalate and phosphate to steady-state levels of greater than 100 nmol/mg protein, and the accumulated Ca2+ could be largely released by ionophore A23187. Inositol 1,4,5-trisphosphate, in a dose-dependent manner (0.5-5.0 microM), caused the rapid release (less than 5 s) of 40-70% of the total A23187-releasable store of accumulated Ca2+. The membrane vesicles that release accumulated Ca2+ in response to inositol 1,4,5-trisphosphate were enriched in enzymes characteristically found in smooth endoplasmic reticulum. These results support the hypothesis that inositol 1,4,5-trisphosphate, produced by the hydrolysis of phosphatidylinositol 1,4-bisphosphate in response to stimulation of cell surface receptors, is a second messenger mediating the release of Ca2+ from intracellular storage sites.