The cholinergic system

Acetylcholine is synthesized in the nerve ending of the pre-synaptic nerve from choline and acetyl coenzyme A. The reaction is catalysed by the enzyme choline acetyltransferase. 

Acetylcholine is incorporated into membrane-bound vesicles. 

The arrival of a nerve signal leads to the release of acetylcholine. The mechanism of this process is poorly understood. Conventionally, it is thought that vesicles containing the neurotransmitter merge with the cell membrane and in doing so release the transmitter into the synaptic gap. Other mechanisms have been proposed however. 

Acetylcholine crosses the synaptic gap and binds to the cholinergic receptor leading to stimulation of the second nerve. 

Acetylcholine moves to an enzyme called acetylcholinesterase which is situated on the postsynaptic nerve and which catalyses the hydrolysis of acetylcholine to produce choline and ethanoic acid. 

---

Basu, N., Scheuhammer, A.M., and Rouvinen-Watt, K. et al. (2006). Methyl mercury impairs components of the cholinergic system in captive mink. Toxicology Science 91,... 

Basu N, Scheuhammer AM, Rouvinen-Watt K, Grochowina N, Klenavic K, Evans RD, Chan HM. 2006. Methyhnercury impairs components of the cholinergic system in captive mink (Mustela vison). Toxicol Sci 91 202-209. 

Describe how changes in the cholinergic system relate to the neurocognitive and behavioural aspects of Alzheimer s disease. 

The cholinergic system has also been implicated in schizophrenia 883... 

The cholinergic system has also been implicated in schizophrenia. Cigarette smoking is remarkably prevalent among patients suffering from schizophrenia. Speculating that this may reflect a form of self-medication, Freedman and colleagues demonstrated that nicotine improved the... 

Lawrence AD, Sahakian BJ. (1995). Alzheimer disease, attention, and the cholinergic system. Alzheimer Dis Assoc Disord. 9(suppl 2) 43-49. 

Domino EF. (1981). Cannabinoids and the cholinergic system. J Clin Pharmacol. 21(8-9 suppi) 249S-55S. 

There is also evidence that the density of muscarinic receptors is increased in limbic regions of depressed patients who have committed suicide. If it is assumed that such a change reflects an increased activity of the cholinergic system, it could help to explain the reduced noradrenergic function as there is both clinical and experimental evidence to suggest that increased central cholinergic activity can precipitate depression and reduce noradrenergic activity. 

Unlike the biogenic amines, the cholinergic system has received relatively little attention as a possible factor in mania. Experimental evidence shows... 

It is expected that severe exposure would produce a broad spectrum of clinical effects indicative of massive overstimulation of the cholinergic system including headache, weakness, dizziness, blurred vision, respiratory difficulty, paralysis, convulsions, and coma. 

Purkerson-Parker S, McDaniel KL, Moser VC Effects of developmental exposure to heptachlor on the cholinergic system in rats. Toxicologist 66(1-S) 131, 2002... 

Figure 2. The cholinergic system in the human brain. The two principal pathways projecting from discrete nuclei are shown as basal forebrain (continuous lines) and pedunculopontine/dorsal tegmental (dotted lines).

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.

---