Cholinergic system receptors

Bielarczyk H, Tomsig JL, Suszkiw JB. 1994. Perinatal low-level lead exposure and the hippocampal cholinergic system selective reduction of muscarinic receptor and cholineacetyltransferase in the rat septum. Brain Res 643 211-217. 

Muscarinic receptors have modulatory effects on numerous other neurotransmitters in the brain (van der Zee and Luiten 1999). Of particular interest are interactions between glutamate and cholinergic systems in learning and memory (Aigner 1995). 

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. 

The central cholinergic system has been implicated in the pathogenesis of affective disorder and in memory function, which is frequently found to be malfunctioning in depressed patients. The memory deficit elicited by chronic ECT in both patients and animals may be related to the decreased density and function of central muscarinic receptors, but it should be emphasized that the changes reported in cholinergic function are small and their relevance to the clinical situation remains to be established. 

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.

Recent research has indicated select abnormalities in the cholinergic system (Perry et al., 2001). Although previously unexamined neurochemically, there was an indication that the cholinergic system may be involved in autism, with abnormalities reported in neurons in the basal forebrain (Bauman Kemper, 1994). Perry et al. (2001) found extensive loss of high affinity nicotinic receptors from the neocortex (frontal and parietal), and from the cerebellum (Lee, et al., in preparation). Nicotinic receptors are implicated in attention, and also consciousness as many general anaesthetics block the receptor channel (Chapter 9). 

There is considerable diversity among nicotinic acetylcholine receptors, and at least one source of this diversity is the multiplicity of acetylcholine receptor genes. Cholinergic-nicotinic receptors in skeletal muscle are different from those in autonomic ganglia and the central nervous system. 

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