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

Abstract

Mammalian organisms posses two cholinesterases: acetylcholinesterase (AChE, EC 3.1.1.7.) and butyrylcholinesterase (BuChE, EC 3.1.1.8.). A clear explanation for this dual expression of acetylcholine-hydrolyzing enzymes is still missing. Better knowledge on how these two enzymes respond to various physiological or pharmacological factors would importantly contribute to the understanding of their function. The aim of the present study is to elucidate 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 response. At this stage, liver and brain were isolated and AChE and BuChE activities were determined in their homogenates. A new approach, based on precise radiometric measurements of AChE and BuChE activities in the polysomal fractions, prepared under non-denaturing conditions, was used to study GC influences on the early stages of biosynthesis of both enzymes. We found a differential GC influence on AChE and BuChE. In brain, only BuChE activity was affected (−30%), while AChE remained practically unchanged. In liver, BuChE activity fell by 60%, while AChE lost only 18% of its control activity. In case of BuChE, decreased activities in the whole homogenates correlated with decreased activities in the polysomal fractions, suggesting that early stages of enzyme biosynthesis were primarily affected. On the other hand, decreased AChE activity in liver homogenates was not paralleled by a significant change at the level of polysomal AChE activity in this organ, suggesting that higher AChE turn-over is primarily responsible for the decreased activity in homogenate. These results, together with the GC-mediated elimination of the correlation between brain and liver BuChE activities, strongly support the proposal of Edwards and Brimijoin (J.A. Edwards, S. Brimijoin, Effects of hypophysectomy on acetylcholinesterase and butyrylcholinesterase in the rat, Biochem. Pharmacol. 32 (1983) 1183–1189) that BuChE is regulated by systemically acting factors, including various hormones, while regulation of AChE is primarily tissue-specific.