Modulation of choline acetyltransferase synthesis by okadaic acid, a phosphatase inhibitor, and KN-62, a CaM kinase inhibitor, in NS-20Y neuroblastoma

Choline-O-acetyltransferase (ChAT) is the enzyme which catalyses the biosyn thesis of the neurotransmitter acetylcholine in cholinergic neurons. Here w e show that in mouse cholinergic NS-20Y neuroblastoma cells cultured in the presence of either okadaic acid (serine/threonine phosphatases 1 and 2A in hibitor) or KN-62 (CaM kinase inhibitor) ChAT activity and mRNA either incr eased or decreased as a function of the drug concentration, respectively. A fter 24 h exposure, okadaic acid exerted a dramatic effect on cell morpholo gy; cells became round and had no more neurites. On the contrary, KN-62 ind uced a slight morphological differentiation of the cells. The present results suggest that phosphatases 1 and 2A and CaM kinase could mediate regulation of ChAT gene expression. (C) 2000 Elsevier Science Ltd. All rights reserved.