CHOLINESTERASES REGULATE NEURITE GROWTH OF CHICK NERVE-CELLS IN-VITROBY MEANS OF A NONENZYMATIC MECHANISM

Cholinesterases present homologies with some cell adhesion molecules; however, it is unclear whether and how they perform adhesive functions . Here, we provide the first direct evidence showing that neurite grow th in vitro from various neuronal tissues of the chick embryo can be m odified by some, but not all, anticholinesterase agents. By quantifyin g the neuritic G4 antigen in tectal cell cultures, the effect of antic holinesterases on neurite growth is directly compared with their choli nesterase inhibitory action. BW 284C51 and ethopropazine, inhibiting a cetylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectiv ely, strongly decrease neurite growth in a dose-dependent manner. Howe ver, echothiophate which inhibits both cholinesterases, does not chang e neuritic growth. These quantitative data are supplemented by morphol ogical observations in retinal explant cultures grown on striped lamin in carpets, viz., defasciculation of neurite bundles by BW 284C51 and Bambuterol occurs, indicating that these drugs disturb adhesive mechan isms. These data strongly suggest that a) cholinesterases can particip ate in regulating axonal growth, b) both AChE and BChE can perform suc h a nonsynaptic function, and c) this function is not the result of th e enzyme activity per se, since at least one drug was found that inhib its all cholinesterase activities but not neurite growth. Thus, a seco ndary site on cholinesterase molecules must be responsible for adhesiv e functions.