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.
Cowburn
R F
RF
Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, NOVUM, Huddinge, Sweden.
Wiehager
B
B
Sundström
E
E
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects*; D013268:Stimulation, Chemical
D016229:Amyloid beta-Peptides; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D010455:Peptides; D018160:Receptors, Cytoplasmic and Nuclear; C061107:inositol-1,3,4,5-tetrakisphosphate receptor; C081655:inositol-1,3,4,5-tetrakisphosphate; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium