Release of Acetylcholinesterase from Nigro-Striatal Neurons

Abstract

It is well established that acetylcholinesterase (AChE) is an ectoenzyme that hydrolyses acetylcholine (ACh) (see Bon, this volume). However AChE is polymorphic (see Vigny, this volume) and in both the periphery (Chubb and Smith 1975a) and in the brain (Chubb et al. 1976), some forms of the enzyme are soluble. Why should this be so? Since soluble AChE is intracellular (Somogyi et al. 1975), it could presumably have a function inside the cell, i.e. function as an endoenzyme. It would thus be playing a role other than its familiar one in cholinergic transmission (cf. Millar and Chubb 1984). Alternatively, soluble AChE could be released. Of the five soluble isoenzymes of AChE, one has been shown to be secreted from the adrenal gland in a K+-evoked, Ca++-dependent manner (Chubb and Smith 1975b). This same form of the enzyme is detectable in cerebrospinal fluid (CSF) and appears to be derived from the brain as a physiological process (Chubb et al. 1976). Hence, AChE not only exists as an ectoenzyme but perhaps also as an endoenzyme and secretory neuroprotein. Over the last few years we have been learning more about the release of AChE. Levels of AChE in CSF are markedly reduced following destruction of a particular region of the brain, the substantia nigra (Greenfield and Smith 1979). Hence, it is possible that AChE is normally released from nigral neurons. In this chapter I shall review the evidence that within the substantia nigra AChE is released specifically from the cells that project to the striatum (nigrostriatal neurons) and explore the possibility that the phenomenon is unrelated to cholinergic transmission.