The inositol 1,4,5-trisphosphate receptor: kinetic properties and regulation
| Autor: | Jean-Pierre Mauger, Jean-Philippe Lièvremont, France Piétri-Rouxel, Mauricette Hilly, Jean-François Coquil |
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| Rok vydání: | 1994 |
| Předmět: |
inorganic chemicals
endocrine system Receptors Cytoplasmic and Nuclear Inositol 1 4 5-Trisphosphate Endoplasmic Reticulum Biochemistry Second Messenger Systems chemistry.chemical_compound Endocrinology Animals Inositol 1 4 5-Trisphosphate Receptors Inositol Phosphatidylinositol Rats Wistar Receptor Inositol phosphate Molecular Biology chemistry.chemical_classification Cell Membrane Rats carbohydrates (lipids) Cytosol Kinetics chemistry Liver embryonic structures Second messenger system Calcium Female sense organs Calcium Channels Signal transduction Intracellular |
| Zdroj: | Molecular and cellular endocrinology. 98(2) |
| ISSN: | 0303-7207 |
| Popis: | Inositol 1,4,5-trisphosphate (InsP3) is a second messenger responsible for the mobilization of intracellular Ca2+ after receptor-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate. InsP3 binds to a specific receptor located on the membrane of an intracellular compartment and opens a Ca2+ channel causing the cytosolic Ca2+ concentration to increase. Measurement of radiolabelled InsP3 binding and InsP3-induced Ca2+ release in parallel experiments indicated that the liver InsP3 receptor exists in two main states: an active state (A) and an inactive one (I). The “I” form of the receptor is found in the presence of high Ca2+ concentrations (above 1 μM). The binding properties of the “A” and the “I” states of the receptor have been characterized by analysing a membrane fraction enriched in InsP3 receptors. The inactive “I” state displays a high affinity (Kd = 2 nM) and slow rates of association and dissociation. The active state “A” of the receptor displays complex kinetic properties. The rate of association and the rate of dissociation of labelled InsP3 are rapid phenomena probably involving several components. The apparent Kd for the InsP3 binding is about 40 nM in a low Ca2+ medium. The affinity of the “A” state of the receptor is increased by Ca2+ (at concentrations lower than 0.5 μM) and by thiol reagents. The increase of the affinity of the receptor is due to a decrease of the dissociation rate constants. This lowers the threshold such that Ca2+ is released at lower concentrations of InsP3. These data indicate that the binding of InsP3 to its receptor is a complex phenomenon involving the transition among several states. These changes in the receptor properties may be involved in the mechanisms underlying the positive and negative feedback for the InsP3-induced Ca2+ release found in several cell types. |
| Databáze: | OpenAIRE |
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