beta-Amyloid peptides enhance binding of the calcium mobilising second messengers, inositol(1,4,5)trisphosphate and inositol-(1,3,4,5)tetrakisphosphate to their receptor sites in rat cortical membranes.

We studied the effects of the beta-amyloid (A beta) peptides A beta-(1-40), A beta-(25-35-NH2) and A beta-(25-35-COOH) on binding of the phosphoinositide derived, calcium mobilising, second messengers inositol(1,4,5)-trisphosphate (Ins(1,4,5)P3) and inositol(1,3,4,5)-tetrakisphosphate (Ins(1,3,4,5)P4) to their receptor sites in rat cerebral cortical membranes. All three peptides gave statistically significant dose-dependent increases in both [3H]Ins(1,4,5)P3 and [3H]Ins(1,3,4,5)P4 binding. A beta-(1-40) and A beta-(25-35-NH2) enhanced [3H]Ins(1,4,5)P3 and [3H]Ins(1,3,4,5)P4 binding to a similar extent. In comparison, A beta-(25-35-COOH) gave much greater enhancements of [3H]Ins(1,4,5)P3 and [3H]Ins(1,3,4,5)P4 binding. However, a component of the latter appeared to be due to the formation of pelletable A beta-(25-35-COOH)/[3H]Ins(1,3,4,5)P4 aggregates, that occurred in the absence of membranes. These results raise the possibility that A beta affects calcium homeostasis by a direct action on [3H]Ins(1,4,5)P3 and [3H]Ins(1,3,4,5)P4 receptor sites.