AMYLOID-BETA PROTEIN (25-35) STIMULATION OF PHOSPHOLIPASES A, C AND DACTIVITIES OF LA-N-2 CELLS

[H-3]Myristic acid prelabeled LA-N-2 cells were exposed to varying con centrations of amyloid beta protein (25-35), from 20 to 250 mu g/ml, a nd the activation of phospholipases A and D estimated. A progressive i ncrease in phosphatidylethanol formation, a measure of phospholipase D activity, and of free fatty acid release, a measure of phospholipase A activity, was observed over a time-course of 60 min. [H-3]Inositol p relabeled LA-N-2 cells mere exposed to varying concentrations of A bet a P, from 20 to 125 mu g/ml, and phospholipase C activation was measur ed, There was an increased release of inositol phosphates in the prese nce of amyloid beta protein as a function of incubation time. The effe cts of adrenergic, metabotropic amino acid and bombesin antagonists on the A beta P mediated stimulation of phospholipase C activity was inv estigated, Propranolol, a beta adrenergic antagonist, 7-chlorokynureni c acid, a metabotropic amino acid antagonist, and [Tyr(4)-D-Phe(12)] b ombesin, a bombesin antagonist, blunted the A beta P stimulation of ph ospholipase C activity in [H-3]inositol prelabeled LA-N-2 cells, This suggests that amyloid beta protein activation of phospholipase C may b e receptor mediated, The phospholipase C inhibitor U 71322 prevented t he activation of phospholipase C by A beta P, However, this activation was not effected by tocopherol, propylgallate, or vitamin C.