Studies of the cholinesterase of sheep brain and concomitant protein.

Acetylcholine was first synthesized by Baeyer in 1867. At the same time it was only of chemical interest but decades later its powerful pharmacological effects were noted: Hunt and Taveau pointed out the role of acetylcholine in lowering blood-pressure (1). Dale and his co-workers demonstrated that acetylcholine is a chemical mediator of the nerve impulses at parasympathetic endings (2). Thus the notion of chemical mediation that had been introduced by Elliot in respect of adrenalin (3) was extended to the physiology of ganglionic synapses and neuromuscular junctions (4). This hypothesis met with some opposition among neurophysiologists; objections to it were reviewed by Eccles (5). For example stransmission or nerve impulses across the neuromuscular junctions and synapses occurs within milliseconds and chemical mediation by acetylcholine cannot explain this phenomenon. Fulton (6) and Erlanger (7) considered the extremely short interval for the effect of the axon-potential which would preclude the intervention of any process dependent upon substances released at the nerve endings. Early hypotheses of chemical mediation were based on experiments which employed methods of classical physiology and saccording to Naohmansohn and his co-workers, did not permit an interpretation of the precise function of the ester in the physiochemical mechanism of the propogation of nerve impulses. Using suitable methods for recording cellular functions such as conduction of nerve impulses (8,9), Nachmansohn and his school came to the following conolusions(10): The ester is released at the neuronal surface when a stimulus reaches the nerve cell. Bythe action of acetylcholine the permeability of the membrane to ions is increased and depolarization ' Occurs. The depolarized point becomes negative to the adjacent region and a flow of current is generated. This flow of current transmits the impulse to a neighbouring point where more acetylcholine is released. The process is repeated and in this way the impulse is propagated. As the propagation of the nerve impulse hinges. on the release and disappearance of the ester, the enzyme responsible for the catalysis of the latter reaction attracted interest. The aim of the work described in this part of the Thesis was to isolate or purify the acetylcholine hydrolysing enzyme of the sheep brain, a material which had received little attention so far. The question whether the tissue chosen was suitable for the isolation of the enzyme may be considered through a brief survey of the distribution of the enzyme.