Acetylcholine/cholinergic system metabolism

In Chapter 8, peripheral aspects of the cholinergic system were considered. The basics of the neuron (Fig. 8-1), specifically the cholinergic neuron (Fig. 8-5), the synapse (Fig. 8-2), and depolarization (Fig. 8-3), were also presented. The significance and chemistry of acetylcholine (ACh) was discussed. Chapter 9 continued with the remainder of the peripheral autonomic nerve plan (i.e., the sympathetic, or adrenergic, system). The biosynthesis of the catecholamines DA, NE, and EP were discussed and illustrated (Fig. 9-1), and the metabolism schemes for NE and EP (Fig. 9-3) and DA (Fig. 9-4) were outlined. Much of the early (before 1960) neurochemistry elucidated, and neurotransmitters identified, were central to the functioning of the peripheral nervous system. 

The main toxic effect of the OPs is the inhibition of the acetylcholine esterase (AChE) in the synapses and neuromuscular junctions, causing cholinergic crisis, which eventually leads to seizures, respiratory arrest and death. There are considerable differences in the dynamic of clinical manifestations and impairment induced by nerve agents and OP insecticides (slower onset, dependent on metabolic activation, prolonged effect based on their accumulation in certain tissues and subsequent systemic release). 

Costa, E., Tagliamonte, N., Brunello, N., and Cheney, D.L., Effects of stress on the metabolism of acetylcholine in the cholinergic pathways of extra pyramidal and limbic systems, in Catecholamines and Stress Recent Advances, Usdin, E., Kvetnansky, R., and Kopin, I. J., Eds., Elsevier, New York, 1980, 59. 

A study of the distribution, in the mammalian central nervous system, of the various substances discussed in this review reveals that none—except y-aminobutyric acid which has general metabolic as well as humoral functions—is as widespread as acetylcholine and there is no general tendency for fibres deficient in acetylcholine to contain correspondingly large amounts of any of the other substances. This is an important point, since the non-cholinergic excitatory transmitter should be found in at least a number of acetylcholine-free nerve tracts. Instead, it appears that some areas of the nervous system contain a multiplicity of humoral substances while others have none at all. 

---