beta-amyloid(25-35) inhibits the activity of inositol(1,4,5)-trisphosphate-5-phosphatase

beta-amyloid (A beta) peptides are known to disrupt calcium homeostasis in cells. In the present study, the effects of A beta(25-35) upon the activity of soluble Ins(1,4,5)P-3-5-phosphatase have been investigated. A beta(25-3 5) inhibited, and dithiothreitol (DTT) increased the activity of soluble ra t cerebellar Ins(1,4,5)P-3-5-phosphatase. The change in activity was not ac companied by an obvious change in the sensitivity of the Ins(1,4,5)P-3-5-ph osphatase to inhibition by glucose-6-phosphate or phytic acid. A beta(35-25 ) also inhibited soluble Ins(1,4,5)P-3-5-phosphatase activity, but at a low er potency than A beta(25-35). It is concluded that A beta(25-35) affects t he metabolism of Ins(1,4,5)P-3 although the potency is not sufficiently hig h to contribute to any significant extent to the effects of this peptide up on calcium homeostasis.