CHARACTERIZATION OF THE ACETYLCHOLINE-REDUCING EFFECT OF THE AMYLOID-BETA PEPTIDE IN MOUSE SN56 CELLS

We previously reported that the amyloid-beta protein (A beta) reduces the synthesis of acetylcholine (ACh) in a mouse septal cell line, SN56 , without causing death of the cells. Here, we report that the ACh-red ucing effect of either A beta 1-28 or A beta 1-42 (100 nM; 48 h) in SN 56 cells can be prevented by a co-treatment with the tyrosine kinase i nhibitors, genistein (75 mu M) and tyrphostin A25 (50 mu M). Treatment of the cells with either of these inhibitors alone increased ACh leve ls. An enhancement of the cellular ACh content was also obtained with aphidicolin, a compound which inhibits DNA synthesis. However, co-trea tment of the cells for 48 h with aphidicolin (500 nM) and A beta 1-42 (100 nM) did not prevent the reduction in ACh levels caused by the pep tide. Furthermore, this effect could not prevented by a pre-treatment with vitamin E (50 mu g/ml). These results suggest that the ACh-reduci ng effect of A beta in SN56 cells is dependent on tyrosine phosphoryla tion, but is not dependent on DNA synthesis and may not be mediated by free radicals. (C) 1997 Elsevier Science Ireland Ltd.