AMYLOID-BETA PROTEIN-(25-35) STIMULATION OF PHOSPHOLIPASE-C IN LA-N-2CELLS

The amyloid beta protein (25-35) stimulated appearance of H-3-inosilol phosphates from [H-3] inositol-prelabeled LA-N-2 cells was investigat ed. This stimulation was unaltered by extra- and intracellular calcium chelators in a calcium-free medium or by several protein kinase inhib itors. This phospholipase C stimulation by amyloid beta protein appear ed to be pertussis toxin sensitive. It is possible that this phospholi pase C stimulation by amyloid beta protein is a receptor-mediated proc ess. This possibility is based on two related observations. The stimul ation is ablated by the presence of conventional antagonists for metab otropic, adrenergic, and bombesin agonists. The IC50 values were 12 mu M for propranolol, 15 mu M for AP-3, and 25 nM for [Tyr(4),D-Phe(12)] bombesin. Additional support comes from results of densensitization a nd resensitization experiments. Amyloid beta protein stimulation of ph ospholipase C was absent from LA-N-2 cells previously treated with nor epinephrine, trans-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD), bombesin, or amyloid beta peptide. In a similar manner, LA-N-2 cells previously treated with amyloid beta protein were no longer responsive to norepinephrine, t-ACPD, or bombesin. The responsiveness to amyloid beta protein returned, subsequent to a period of resensitization for the individual agonists. It is suggested that this observed amyloid be ta protein stimulation of phospholipase C may be responsible for the e levated quantity of inositol seen in the brains of Alzheimer's disease patients.