Acetylcholinesterase tissue distribution

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. 

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. 

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... 

Fish rapidly absorb, metabolize, and excrete chlorpyrifos from the diet. The mechanism of action of chlorpyrifos occurs via phosphorylation of the active site of acetylcholinesterase after initial formation of chlorpyrifos oxon by oxidative desulfuration. In studies with chaimel catfish (Ictalurus punctatus), the oral hioavailability of chlorpyrifos was 41%, substantially higher than in mammals. Catfish muscle contained less than 5% of the oral dose with an elimination half-life (Tbl/2) of 3.3 days. Chlorpyrifos residues in whole catfish were more than 95% chlorpyrifos, while bile and urine primarily contained metabolites. The dephosphorylated metabolite trichloropy-ridinol (TCP) was the major metabolite in the blood while the glucuronide conjugate of TCP was the major metabolite in mine and bile. The toxic metabolite, chlorpyrifos oxon, was not detected in blood, tissues, or excreta. Extensive metabolism resulted in a low potential for chlorpyrifos to accumulate in catfish from dietary exposure. In both fish and mammals, TCP is a major biotransformation product. Chaimel catfish rapidly distribute waterborne chlorpyrifos into the blood and more slowly to peripheral tissues, with concentrations highest in fat and lowest in muscle. As was true with dietary chlorpyrifos, TCP was the major metabolite in blood and the glucuronide conjugate of TCP was the major metabolite in urine and bile. Pharmacokinetics and metabolism of waterborne chlorpyrifos in channel catfish were similar to the disposition of chlorpyrifos in other vertebrates. 

One of the pillars upon which rests the prevailing theory of the chemical mediation of nerve impulses is the uniqueness, in conducting tissue, of the enzyme that hydrolyzes acetylcholine. The characteristics of acetylcholinesterase that distinguish it from the other cholinesterases are as follows (1) A small Km when acetylcholine is the substrate. (2) Inhibition of the hydrolysis of acetylcholine by the substrate so that when the velocity is plotted against substrate concentration a bell-shaped curve results. (3) A rate of hydrolysis that is greatest with acetylcholine, less with propionylcholine, and the least with butyrylcholine. None of these properties is shared by the other cholinesterases. Acetylcholinesterase occurs, however, not only in conducting tissue but also in erythrocytes and cobra venom. The distribution of cholinesterases has been reviewed by Augustinsson. ... 

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