Glucocorticoids differentially control synthesis of acetylcholinesterase and butyrylcholinesterase in rat liver and brain

Mammalian organisms posses two cholinesterases: acetylcholinesterase (AChE, EC 3.1.1.7.) and butyrylcholinesterase (BuChE, EC 3.1.1.8.). A clear expla nation for this dual expression of acetylcholine-hydrolyzing enzymes is sti ll missing. Better knowledge on how these two enzymes respond to various ph ysiological or pharmacological factors would importantly contribute to the understanding of their function. The aim of the present study is to elucida te glucocorticoid (GC) influences on the synthesis of AChE and BuChE in rat liver and brain. Female Wistar rats were treated with dexamethasone until body weight loss was greater than 15%, signaling full expression of a GC re sponse. At this stage, liver and brain were isolated and AChE and BuChE act ivities were determined in their homogenates. A new approach, based on prec ise radiometric measurements of AChE and BuChE activities in the polysomal fractions, prepared under non-denaturing conditions, was used to study GC i nfluences on the early stages of biosynthesis of both enzymes. We found a d ifferential GC influence on AChE and BuChE. In brain, only BuChE activity w as affected (- 30%), while AChE remained practically unchanged. In liver, B uChE activity fell by 60%, while AChE lost only 18% of its control activity . In case of BuChE, decreased activities in the whole homogenates correlate d with decreased activities in the polysomal fractions, suggesting that ear ly stages of enzyme biosynthesis were primarily affected. On the other hand ; decreased AChE activity in liver homogenates was not paralleled by a sign ificant change at the level of polysomal AChE activity in this organ, sugge sting that higher AChE turn-over is primarily responsible for the decreased activity in homogenate. These results, together with the GC-mediated elimi nation of the correlation between brain and liver BuChE activities, strongl y support the proposal of Edwards and Brimijoin (J.A. Edwards, S. Brimijoin , Effects of hypophysectomy on acetylcholinesterase and butyrylcholinestera se in the rat, Biochem. Pharmacol. 32 (1983) 1183-1189) that BuChE is regul ated by systemically acting factors, including various hormones, while regu lation of AChE is primarily tissue-specific. (C) 1999 Elsevier Science Irel and Ltd. All rights reserved.