Acetylcholinesterase localization

Released ACh is rapidly hydrolyzed and inactivated by a specific acetylcholinesterase, localized to pre- and postjunctional membranes (basal lamina of motor end plates), or by a less specific serum cholinesterase (butyrylcholinesterase), a soluble enzyme present in serum and interstitial fluid. 

Extracellular degradation removes acetylcholine, the neuropeptides and ATP. Acetylcholine is rapidly hydrolyzed to choline and acetate by acetylcholinesterase. The enzyme is localized in both the presynaptic and the postsynaptic cell membrane and splits about 10,000 molecules of acetylcholine per second. 

Carson K.A. and Burd G.D. (1980). Localization of acetylcholinesterase in the main and accessory bulbs of the mouse by light and electron microscopic histochemistry. J Comp Neurol 191, 353-371. 

The special case of the endogenous transmitter acetylcholine illustrates well the high velocity of ester hydrolysis. Acetylcholine is broken down at its sites of release and action by acetylcholinesterase (pp. 100,102) so rapidly as to negate its therapeutic use. Hydrolysis of other esters catalyzed by various esterases is slower, though relatively fast in comparison with other biotransformations. The local anesthetic, procaine, is a case in point it exerts its action at the site of application while being largely devoid of undesirable effects at other locations because it is inactivated by hydrolysis during absorption from its site of application. 

There are two major types of cholinesterases acetylcholinesterase (AChE) and pseudocholinesterase (pseudo-ChE). AChE (also known as true, specific, or erythrocyte cholinesterase) is found at a number of sites in the body, the most important being the cholinergic neuroeffector junction. Here it is localized to the prejunctional and postjunctional membranes, where it rapidly terminates the action of synaptically released ACh. It is essential to recognize that the action of ACh is ter-... 

Another use for acetylcholinesterase inhibitors is in glaucoma, in which high intraocular pressure can lead to permanent damage to the optic disk, resulting in blindness. The local instillation of physostigmine (8.14) or echothiophate (8.19) solution in the eye results in a long-lasting decrease in the intraocular pressure as well as myosis (contraction of the pupil). 

Ravazzolo, R., et al. 1988. Characterization, localization, and biosynthesis of acetylcholinesterase in K562 cells. Arch Biochem Biophys 267 245. 

Succinylcholine, similar to acetylcholine, interacts with the cholinergic receptors at the end plate region of the muscle, resulting in depolarization of the chemically excitable membrane. This, in turn, creates local action potentials, spreading them to and depolarizing the adjacent excitable membranes, finally culminating in a muscle contraction, or fasciculation, which is an uncoordinated muscle contraction. However, unlike acetylcholine, succinylcholine is not metabolized by acetylcholinesterase, and hence causes persistent depolarization of the end plate. The continuous presence of succinylcholine leads to inexcitability of the membrane adjacent to the end plate, resulting in... 

Lan CT, Shieh JY, Wen CY, Tan CK, Ling EA. 1996. Ultrastruc-tural localization of acetylcholinesterase and choline acet-yltransferase in oligodendrocytes, glioblasts and vascular endothelial cells in the external cuneate nucleus of the gerbil. Anat Embryol (Berl) 194 177-185. 

Gmhic, Z., Sketelj, J., Klinar, B., Brzin, M. (1981). Recovery of acetylcholinesterase in the diaphragm, brain, and plasma of the rat after irreversible inhibition by soman a study of cyto-chemical localization and molecular forms of the enzyme in the motor end plate. J. Neurochem. 37 909-16. 

Rossi, S.G., Dickerson, I.M., Rotundo, R.L. (2003). Localization of the calcitonin gene-related peptide receptor complex at the vertebrate neuromuscular junction and its role in regulating acetylcholinesterase expression. J. Biol. Chem. 278 24994— 25000. 

The enzyme acetylcholinesterase (AChE) is localized at the synapse and degrades ACh released by the presynaptic nerve, thus limiting its actions. Inhibition of the effects of AChE (e.g. with a cholinesterase inhibitor such as physo-stigmine) prolongs the time course of action of ACh or of stimulation of the presynaptic nerve. 

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