Acetylcholinesterase distribution

Figure 10.1-12. Distribution of compounds in the layer of acetylcholinesterase inhibitors neurons colored m black and marked with a circle contain i inhibitors of acetylcholinesterase, and neurons in light gray contain other compounds.

Neurokinin effects are terrninated by proteolysis. In vitro acetylcholinesterase (ACE) and enkephalinase can hydrolyze substance P. However, there appears to be no clear evidence that either acetylcholinesterase or ACE limit the actions of released substance P. Enkephalinase inhibitors, eg, thiorphan, can augment substance P release or action in some systems but the distribution of enkephalinase in the brain does not precisely mirror that of substance P. There appears to be a substance P-selective enzyme in brain and spinal cord. 

Alternatively, some studies used expert opinion to extrapolate the effectiveness of donepezil over a longer period (Neumann et al, 1999 O Brien et al, 1999). However, it is recognized that expert opinion can be the weakest source of evidence, which introduces considerable uncertainty into the analysis and interpretation of the results. In addition, the cost-effectiveness of acetylcholinesterase inhibitors depends heavily on the distribution of the cohort of patients across different severity states. O Brien s team found that the results of their model were very sensitive to this variable. In this context, the correct... 

Crespo C., Brinon J.G., Porteros A., Arevalo R., et al. (1999). Distribution of acetylcholinesterase and choline acetyltransferase in the main and accessory olfactory bulbs of the hedgehog (Erinaceus europaeus). J Comp Neurol 403, 53-67. 

Two types of OPIDN have been described in animals (Abou-Donia and Lapadula 1990). Type I is produced by compounds with a pentavalent phosphorus (like TOCP), and Type II is produced by compounds with a trivalent phosphorus. Characteristics used to differentiate between the types of OPIDN include species selectivity, age sensitivity, length of latent period, and morphology of neuropathologic lesions. Thus, at doses that did not produce death due to acetylcholinesterase inhibition, TOCP (a Type I compound) produced lesions in the spinal cord of rats without producing ataxia. In contrast, triphenyl phosphite (a Type II compound) produced delayed (1 week) ataxia in the rat and a distribution of spinal cord lesions distinct from those produced by TOCP (Abou-Donia and Lapadula 1990). 

Jbilo, O., Bartels, C.F., Chatonnet, A., Toutant,J.P. and Lockridge, O. (1994) Tissue distribution of human acetylcholinesterase and butyrylcholinesterase messenger RNA. Toxicon 32, 1445-1457. 

Toutant, J.-P. (1989) Insect acetylcholinesterase catalytic properties, tissue distribution and molecular forms. Progress in Neurobiology 32, 423 46. 

Cholinesterases are widely distributed throughout the body in both neuronal and non-neuronal tissues. Based largely on substrate specificity, the cholinesterases are subdivided into the acetylcholinesterases (AChEs) (EC... 

It is well established that acetylcholine can be catabolized by both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) these are also known as "true" and "pseudo" cholinesterase, respectively. Such enzymes may be differentiated by their specificity for different choline esters and by their susceptibility to different antagonists. They also differ in their anatomical distribution, with AChE being associated with nervous tissue while BChE is largely found in non-nervous tissue. In the brain there does not seem to be a good correlation between the distribution of cholinergic terminals and the presence of AChE, choline acetyltransferase having been found to be a better marker of such terminals. An assessment of cholinesterase activity can be made by examining red blood cells, which contain only AChE, and plasma. 

The more widely distributed butyrylcholinesterase612 is less specific but prefers butyrylcholine. Acetylcholinesterase is a very efficient catalyst 613-615 /ccat = 1.6 x 104 s-1... 

A. Modes of Toxic Action. This includes the consideration, at the fundamental level of organ, cell and molecular function, of all events leading to toxicity in vivo uptake, distribution, metabolism, mode of action, and excretion. The term mechanism of toxic action is now more generally used to describe an important molecular event in the cascade of events leading from exposure to toxicity, such as the inhibition of acetylcholinesterase in the toxicity of organophosphorus and carbamate insecticides. Important aspects include the following ... 

Rachinsky, T. L, Camp, S., Li, Y., Ek-strom, J., Newton, M., Taylor, P. Molecular Cloning of Mouse Acetylcholinesterase Tissue Distribution of Alternatively Spliced mRNA Species. Neuron 1990, 5, 317-327. 

In the clinic, esmolol s distribution half-life is 2 min and its elimination half-life is 9 min. Esmolol hydrochloride is rapidly metabolized by hydrolysis of the ester linkage, chiefly by esterases in the cytosol of red blood cells and not by plasma cholinesterases or red cell membrane acetylcholinesterase [22]. Its volume of distribution is 3.4 L kg-1, and its total clearance is 285 mL kg-1 min-1, "... which is greater than cardiac output thus the metabolism ofesmolol is not limited by the rate of blood flow to metabolizing tissues such as the liver or affected by hepatic or renal blood flout [22]. As expected from such a "... high rate of blood-based metabolism, less than 2% of the drug is excreted unchanged in the wind [22]. Within 24 h after infusion, approximately... 

Hall, Z.E. (1973). Multiple forms of acetylcholinesterase and their distribution in endplate and nonendplate regions of rat diaphragm muscle. J. Neurobiol. 4 343-61. 

Gmhic, Z., Komel, R., Walker, W.F., Miranda, A.F. (1995). Myoblast fusion and innervation with rat motor nerve alter distribution of acetylcholinesterase and its mRNA in cultures of human muscle. Neuron 14 317-27. 

Rumenjak, V. (1998). Distribution of human erythroc de acetylcholinesterase according to age, sex and pregnancy. Acta Med. Croat. 52 187-9. 

ANTICHOLINESTERASES are agents that inhibit cholinesterases, enzymes that fall into two main families -acetylcholinesterases (AChE) and butyrylcholinesterases (BChE). These enzymes are of related molecular structures but have different distributions, genes and substrate preferences. The enzymes have globular catalytic subunits that are the soluble form of the esterases (as in plasma or CSF), or they can be attached via long collagen tails to the cell membrane. 

Chole- Relating to the biliary system, cholestasis The failure of the normal bile flow to the intestine, causing cholestatic jaundice, cholinergic Nerve fibres that release ACETYLCHOLINE, cholinesterases Enzymes that hydrolyse choline esters, especially ACETYLCHOLINE of which there are two main forms acetylcholinesterase ( true cholinesterase ) is specific for acetylcholine, rapid in this action, and has a discrete distribution being especially located near cholinergic nerve terminals (and in erythrocytes) butyrylcholinesterase ( pseudo cholinesterase) is less selective and is able to hydrolyse some drugs (e.g. SUCCINYLCHOLINE CHLORIDE). Many drugs are known that inhibit the action of these enzymes. See anticholinesterases. chromatin A protein found in the nucleus which stains with basic dyes. It is used in the study of the behaviour of... 

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