Cholinergic nervous system

Acetylcholine receptors have been classified into sub-types based on early studies of pharmacologic selectivity. Long before structures were known, two crude alkaloid fractions, containing nicotine and muscarine (Fig. 11-2), were used to subclassify receptors in the cholinergic nervous system (Fig. 11-3). The greatly different... 

Following his extensive studies of nicotine, curare, and other chemicals acting on what is now known as the cholinergic nervous system, John Langley hypothesized that there must be receptive substances present in cells to explain the effects of nicotine alone and in combination with other chemicals. He wrote Since the accessory substance is the recipient of stimuli which it transfers to the contractile material, we may speak of it as the receptive substance (italics in original) of the muscle (Langley 1905). These conclusions followed from observations... 

Holte, HR., Eriksen, S., Skulberg, O., and Aas, P 1998. The effect of water soluble cyanotoxin(s) produced by two species of Anabaena on the release of acetylcholine from the peripheral cholinergic nervous system of the rat airway. Environ Toxicol Pharmacol 5, 51-59. 

Cooper, J.R. (1994). Unsolved problems in the cholinergic nervous system. J. Neurochem. 63 395-9. 

Currently, the most important anticonvulsant is diazepam. The combination of atropine and diazepam is more effective in reducing mortality than atropine or oxime alone. It was also shown that diazepam enhanced the effieaey of low doses of atropine. In the cholinergic nervous system, diazepam appears to decrease the synaptic release of ACh. The main consequence of the action of benzodiazepines in CNS is hyperpolarization of neurons making them significantly less susceptible to cholinergically indueed depolarization. The ultimate result is cessation of propagation of convulsions (Sellstrom, 1992 Marrs, 2004 Antonijevic and Stojiljkovic, 2007). 

Furthermore, it was observed that the oxime HI-6 might show direct pharmacological effects in the cholinergic nervous system in skeletal muscles. It has been found that HI-6 reduces the miniature endplate potentials and increases the quantal content by a dose-dependent decrease in the miniature endplate potential amplitude (Melchers et al., 1991). Other possible explanations have been suggested for oximes at other targets in the nervous system, such as... 

Acute choline overexposure results in hyperstimulation of the cholinergic nervous system. 

The transmission of impulses throughout the cholinergic nervous system is mediated by acetylcholine (1), and compounds that produce... 

Studies of a large number of compounds have supplied considerable information on structural requirements for cholinergic activity however (especially in the older literature) these data must be interpreted with caution. They have been obtained using a variety of in vivo and in vitro testing procedures and biological preparations in a variety of animal species, and different biological responses associated with stimulation of the cholinergic nervous system were measured. Additionally,... 

Aas, P., The toxic effect of an AChE-inhibitor on the cholinergic nervous system in airway smooth muscle. Toxicology, 49, 91, 1988. 

Dominating signs of poisoning with OP and nerve agents are caused by hyperstimulation of the cholinergic nervous system due to an elevated level of acetylcholine caused by inhibition of AChE (acute cholinergic crisis). 

The enzyme AChE, found at the receptor sites of tissue innervated by the cholinergic nervous system, hydrolyzes ACh very rapidly it has one of the highest enzyme turnover numbers (number of molecules of substrate that it turns over per unit time) known.11 A similar enzyme having ACh as its preferred substrate is found in or on erythrocytes (red blood cells, RBCs) and is known as erythrocyte, or true, ChE (RBC-ChE). Butyrocholinesterase (BuChE, also known as serum or plasma cholinesterase, and as pseudocholinesterase), another enzyme of the ChE family, has butyrylcholine as its preferred substrate. Butyrylcholine is present in plasma or serum and in some tissues. BuChE and RBC-ChE are discussed in the Blood Cholinesterases section below. 

This portion of the cholinergic nervous system can be further subdivided into the muscarinic and nicotinic systems, because the structures that are innervated have receptors for the alkaloids muscarine (mAChR) and nicotine (nAChR), respectively, and can be stimulated by these compounds. Mus-... 

Toxic action of AChE inhlntors. Withcxjt AChE, ACh accumulates and causes excessive synaptic neurotransmitter activity in the parasympathetic (cholinergic) nervous system and at neuromuscular (nicotinic) sites. 

Karchmar, A.G., 2007. Anticholinesterases and war gases. In Karchmar, A.G. (Ed.), Exploring the Vertebrate Central Cholinergic Nervous System Springer, New York, pp. 237-310. (Chapter 7). 

The cholinergic nervous system is a network of neurones spread through both the central and peripheral nervous systems which are characterised by synapses. Transmission of signals within the network is electrical except at the synapses where acetylcholine (ACh) is released to carry the impulses across a small gap to the next neurone or to an effector organ. It is ACh which gives the cholinergic nervous system its name. ACh is only one of the many chemical transmitters in the nervous system, whose function is to act as amplifying relay stations for the nerve impulses from the brain. 

A great deal is known about ACh and the cholinergic nervous system. Detailed accounts of the physiology and pharmacology are beyond the scope of this chapter. Here, we concentrate on the essential function of ACh and cholinergic synapses from the standpoint of how transmission can be intermpted by toxic causes. 

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