[3H]Myristic acid prelabeled LA-N-2 cells were exposed to varying concentrations of amyloid beta protein (25-35), from 20 to 250 micrograms/ml, and the activation of phospholipases A and D estimated. A progressive increase 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. [3H]Inositol prelabeled LA-N-2 cells were exposed to varying concentrations of A beta P, from 20 to 125 micrograms/ml, and phospholipase C activation was measured. There was an increased release of inositol phosphates in the presence of amyloid beta protein as a function of incubation time. The effects of adrenergic, metabotropic amino acid and bombesin antagonists on the A beta P mediated stimulation of phospholipase C activity was investigated. Propranolol, a beta adrenergic antagonist, 7-chloro-kynurenic acid, a metabotropic amino acid antagonist, and [Tyr4-D-Phe12]bombesin, a bombesin antagonist, blunted the A beta P stimulation of phospholipase C activity in [3H]inositol prelabeled LA-N-2 cells. This suggests that amyloid beta protein activation of phospholipase C may be receptor mediated. The phospholipase C inhibitor U 71322 prevented the activation of phospholipase C by A beta P. However, this activation was not effected by tocopherol, propylgallate, or vitamin C.