Abstract
In this study, we report our data on the binding of D-myoinositol(1,4,5)P 3 and of 6-deoxy D-myoinositol(1,4,5)P 3 to a rat parotid microsomal fraction and their effect on Ca 2+ release. The binding affinity and the potency of 6-deoxy Ins(1,4,5)P 3 to induce Ca 2+ release are about 100 times lower than those of Ins(1,4,5)P 3. However, maximal concentrations of both inositol trisphosphates induce similar calcium efflux and present comparable displacement of radioligand binding. Experiments were performed to exclude that the microsomal preparations used display rapid metabolism of Ins(1,4,5)P 3 or 6-deoxy Ins(1,4,5)P 3 during binding and Ca 2+ release. We also report that, in permeabilized rat parotid acini preparations, 6-deoxy Ins(1,4,5)P 3 is about 100 times less potent that Ins(1,4,5)P 3 in inducing Ca 2+ release. These data indicate that removal of the hydroxyl group in position 6 of the Ins(1,4,5)P 3 molecule severely reduces its binding affinity which seems, in a large part at least, responsible for the reported loss of potency in mobilizing Ca 2+. Nevertheless, 6-deoxy Ins(1,4,5)P 3 seems to be a full agonist for the release of Ca 2+.
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