Rapid activation and partial inactivation of inositol trisphosphate receptors by adenophostin A
| Autor: | Adkins, C E, Wissing, F, Potter, B V, Taylor, C W |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
Male
endocrine system Adenosine Cell Membrane Permeability Receptors Cytoplasmic and Nuclear Inositol 1 4 5-Trisphosphate Rats carbohydrates (lipids) Calcium Channel Agonists Kinetics Hepatocytes Animals Inositol 1 4 5-Trisphosphate Receptors Calcium Calcium Channels Calcium Signaling Rats Wistar Ion Channel Gating Research Article Protein Binding |
| Popis: | Adenophostin A, the most potent known agonist of inositol 1,4, 5-trisphosphate (InsP(3)) receptors, stimulated (45)Ca(2+) release from the intracellular stores of permeabilized hepatocytes. The concentration of adenophostin A causing the half-maximal effect (EC(50)) was 7.1+/-0.5 nM, whereas the EC(50) for InsP(3) was 177+/-26 nM; both responses were positively co-operative. In rapid superfusion analyses of (45)Ca(2+) release from the intracellular stores of immobilized hepatocytes, maximal concentrations of adenophostin A or InsP(3) evoked indistinguishable patterns of Ca(2+) release. The Ca(2+) release evoked by both agonists peaked at the same maximal rate after about 375 ms and the activity of the receptors then decayed to a stable, partially (60%) inactivated state with a half-time (t(1/2)) of 318+/-29 ms for adenophostin A and 321+/-22 ms for InsP(3). Dissociation rates were measured by recording rates of InsP(3)-receptor channel closure after rapid removal of agonist. The rate of adenophostin A dissociation (t(1/2), 840+/-195 ms) was only 2-fold slower than that of InsP(3) (t(1/2), 436+/-48 ms). We conclude that slow dissociation of adenophostin A from InsP(3) receptors does not underlie either its high-affinity binding or the reported differences in the Ca(2+) signals evoked by InsP(3) and adenophostin A in intact cells. |
| Databáze: | OpenAIRE |
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