CALCIUM MOBILIZATION EVOKED BY AMYLOID BETA-PROTEIN INVOLVES INOSITOL1,4,5-TRISPHOSPHATE PRODUCTION IN HUMAN PLATELETS

We examined the effects of amyloid beta-protein (A beta) on Ca2+ mobil ization in human platelets. The addition of A beta fragments 25-35 (A beta 25-35) gradually increased the cytoplasmic free Ca2+ concentratio n ([Ca2+](i)). After the maximum response, [Ca2+](i) decreased and the n reached a sustained, higher level of [Ca2+](i). Similar effects were also observed with A beta 1-40, whereas 1-28, 12-28 and 31-35 did not affect the Ca2+ response. In the absence of extracellular Ca2+, A bet a 25-35 caused a transient increase in [Ca2+](i), which returned to th e resting level. U73122, a phospholipase C inhibitor, completely aboli shed Ca2+ mobilization induced by thrombin and A beta 25-35. Furthermo re, A beta enhanced the production of inositol 1,4,5-trisphosphate (IP 3) in platelets. These findings suggest that Ca2+ mobilization induced by A beta 25-35 is due to phospholipase C activation and IP3 producti on.