Acetylcholine/cholinergic system synthesis

Drugs which enhance the activity of the central cholinergic system have been shown to have antimanic effects. Experimental studies have shown that lithium increases acetylcholine synthesis in the cortex, which is... 

Figure 5. Cartoon of a cholinergic synapse showing major steps in the synthesis of acetylcholine. The two major receptor types, the ionotropic nicotinic receptor and the metabotropic muscarinic receptor, are shown (see also Chapter 1). Presynaptic muscarinic (M2) and nicotinic receptors are also depicted. Drugs which have been widely used to manipulate the cholinergic systems, and which are mentioned in the text, include the muscarinic receptor antagonists scopolamine and atropine and the nicotinic receptor agonist nicotine. Anticholinesterases (discussed elsewhere in this volume) include drugs such as physostigmine, rivastigmine, donepezil, and galanthamine.

Effects of triethyllead acetate on the cholinergic system in the brain of the rats were investigated in vitro. At concentrations below 0.1 pM it inhibited the depolarized release of acetylcholine (ACh) from slices of cortex and the synthesis of ACh, while the non-depolarized release of ACh was potent in a dose-dependent manner135. 

Synthesis of acetylcholine Choline is transported from the extracellular fluid into the cytoplasm of the cholinergic neuron by a carrier system that cotransports sodium and can be inhibited by the drug hemicholinium. Choline acetyltransferase (CAT) catalyzes the reaction of choline with acetyl CoA to form acetylcholine in the cytosol. 

FIGURE 5.2 (See color insert following page 46.) Presynaptic and postsynaptic regions of the acetylcholine neuron, emphasizing the synthesis and degradation of acetylcholine and the cholinergic receptor suhtypes (Panel [A]) summary of the peripheral nervous system that utilizes acetylcholine as the transmitter (Panel [ B]). 

Evidence that acetylcholine is a chemical mediator of synaptic transmission elsewhere in the central nervous system is circumstantial but convincing. Acetylcholine is the transmitter substance from motor nerves, preganglionic autonomic fibres and the postganglionic fibres of the parasympathetic system to their respective effector cells. In all these fibres, the activity of choline acetyltransferase (choline acetylase), the enzyme responsible for the synthesis of acetylcholine, is high. Conversely, its activity is negligibly low in sensory nerve fibres and transmission from these fibres is demonstrably non-cholinergic in nature . It is reasonable, therefore, to... 

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