Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ester hydrolysis by acetylcholinesterase (from electric eel, Electrophorus electricus) increased in the presence of low concentrations (ca 10(-7) M) of edrophonium, propidium, d-tubocurarine, gallamine, decamethonium or bis-N-methylacridinium, and decreased at higher concentrations. The overall sensitivity of the substrates to inhibition by the ligands was acetylcholine (Ach) greater than phenylacetate (PA) greater than indophenylacetate (IPA). Complete (saturable) inhibition was unattainable with edrophonium or gallamine for IPA and, to a lesser degree, with propidium for PA. Reaction heats between the enzyme and the ligands (edrophonium, propidium and decamethonium) measured directly in a microcalorimeter revealed binding sites that are different from each other in their interaction energetics.
Gen Pharmacol 1986
PMID:Substrate-ligand interactions with acetylcholinesterase and energetics of binding. 381 38

The innervation of the diaphragm has been studied by three methods--cobalt tracing of the nerves, demonstration of cholinesterase activity and fluorescence microscopy for catecholamines and VIP. The cobalt method reveals the peripheral nerve fibers with a sharpness similar to that shown at the level of the central nervous system where this method has so far been more widely applied. The cobalt method helps to outline the distribution pattern of the nerve fibers and it can be of particular interest at the level of the viscera in order to show the different sources of the axons. Fibers giving a positive response to cholinesterase staining are shown at the level of the motor end plates and surrounding the blood vessels. It is suggested that the axons of phrenic origin contribute to the motor end plates while those coming from the vagus are distributed along the connective tissue surrounding the vascular system. Noradrenergic innervation is scarce, appearing as fine varicosities around the vascular beds. The VIPergic fibers are probably, together with the cholinergic ones, the most widespread. They are distributed among the muscle fascicules as well as being in close connection with the blood vessels.
Gen Pharmacol 1986
PMID:The autonomic innervation of the rat diaphragm. 394 43

The enzymes of the cholinergic system have been investigated in discrete brain regions in mice treated with repeated injection of ethanol. Male mice kept under controlled environmental conditions were treated with ethanol (3 g/kg/day) for 3 days. Animals were sacrificed 1 hr after ethanol injections. Brain regions studied were cerebral cortex, cerebellum, midbrain, hypothalamus, medulla oblongata, amygdala, and hippocampus. The administration of a single dose of ethanol resulted in significant increase (P less than 0.05) in choline acetyltransferase (ChAT) activity in all different brain regions. Repeated injections of ethanol at the 2nd and 3rd day did not result in any further rise in ChAT activity of the brain regions studied except for the midbrain. The results also show that acetylcholinesterase (AChE) activities increased significantly (P less than 0.05) in the pons and hippocampus in acutely ethanol intoxicated animals. The repeated injection of ethanol resulted in significant increase in AChE activities of the cortex and the amygdala. Meanwhile, animals developed tolerance to the hypothermic action of ethanol after ethanol third injection. The results of the present investigation indicate that the rapid development of the hypothermic tolerance to ethanol might be mediated by the brain cholinergic system.
Gen Pharmacol 1985
PMID:Brain cholinergic involvement in the rapid development of tolerance to the hypothermic action of ethanol. 399 82

Redistribution of axonal enzymes as a function of time in vitro was studied in an unbranched segment of frog sciatic nerve. Cholinesterase activity moved peripherally at a rate of 99 mm/day and centrally at 19 mm/day. One-quarter of the total nerve content of the enzyme was estimated to be in motion, one-eighth in each direction. Mitochondrial enzymes (hexokinase and glutamic dehydrogenase) moved peripherally at 20-31 mm/day, centrally at 11-20 mm/day. Only 10% of the total content of these mitochondrial enzymes was in motion. No movement of choline acetylase or 6-phosphogluconic dehydrogenase activity was seen even after 4 days in vitro. However, in a 12 day in vivo experiment choline acetylase moved toward the periphery at a rate of 0.34 mm/day. After a day or so in vitro the distal accumulations of cholinesterase and glutamic dehydrogenase decreased, with a concomitant and quantitatively equivalent increase in enzyme activities at the proximal end of the nerve. It is postulated that during incubation a mechanism for reversing the direction of flow develops in the peripheral stump of the nerve. Vinblastine inhibited central and peripheral flow of both cholinesterase and glutamic dehydrogenase. Movement of cholinesterase was not affected by ouabain, thalidomide, or phenobarbital, nor by K(+) excess (110 mM) or absence.
J Gen Physiol 1972 Oct
PMID:Transport of axonal enzymes in surviving segments of frog sciatic nerve. 411 99

Xylocaine and its derivatives act specifically at the neuromuscular junction within the concentration range 0.05 to 2.0 mM. The charged form is the active form of the drugs. There is no correlation between "local anesthetic" activity and effect at the junction. Like d-tubocurarine, these drugs have little or no effect on quantum content, acetylcholinesterase activity, or the passive impedance of the muscle fiber. Yet they produce end plate potentials characterized by a brief, early component and a late, greatly prolonged component, as does procaine. Analysis of these changes in time course suggests that the drugs have little or no effect before receptors are activated by acetylcholine, but cause a decreased and often greatly prolonged response. Clear structure-activity relations indicate that the receptor to which the drugs bind to produce the prolonged response can be the receptor for acetylcholine. Comparison of the effects of the drugs on the end plate potential and on the response to iontophoretically applied acetylcholine also shows that the effects of Xylocaine depend on the time course of receptor activation and are quite different from the effects of d-tubocurarine.
J Gen Physiol 1968 Jul
PMID:Alteration by xylocaine (lidocaine) and its derivatives of the time course of the end plate potential. 431 45

When a quantum of transmitter is released into a synaptic cleft, the magnitude of the subsynaptic response depends upon how much transmitter becomes bound to receptors. Theoretical considerations lead to the conclusion that if receptor density is normally high enough that most of the quantal transmitter is captured, subsynaptic quantal responses may be insensitive to receptor blockade. The effectiveness of receptor blockers in depressing the subsynaptic response should be diminished by interference with processes that normally dispose of transmitter, but increased if receptor density is reduced. In conformity with equations derived from a simple mathematical model, the apparent potency of (+)-tubocurarine (dTC) to depress the peak height of miniature end-plate currents (MEPCs) in mouse diaphragm was substantially reduced by poisoning of acetylcholinesterase (AChE) and increased by partial blockade of receptors by immunoglobulin G from patients with myasthenia gravis or alpha-bungarotoxin. We calculated from the data that normally capture of quantal acetylcholine (ACh) by receptors is approximately 75% of what it would be if there were no loss of ACh by hydrolysis or diffusion of ACh form the synaptic cleft. This fraction is increased to approximately 90% by poisoning of AChE. Conversely, it normally requires blockade of approximately 80% of receptors-and after AChE poisoning, approximately 90% of receptors-to reduce ACh capture (and MEPC height) by 50%. The apparent potency of dTC to alter MEPC time-course (after AChE poisoning) and to depress responses to superperfused carbachol was much greater than its apparent potency to depress MEPC height, but corresponded closely with the potency of dTC to block receptors as calculated from the action of dTC on MEPC height. These results indicate that the amplitude of the response to nerve-applied acetylcholine does not give a direct measure of receptor blockade; it is, in general, to be expected that an alteration of subsynaptic receptor density may not be equally manifest in responses to exogenous and endogenous neurotransmitter.
J Gen Physiol 1981 Sep
PMID:Relation between subsynaptic receptor blockade and response to quantal transmitter at the mouse neuromuscular junction. 612 Feb 8

Miniature endplate currents (MEPCs) recorded from mouse diaphragms with a point voltage clamp, without inhibition of acetylcholinesterase (AChE) and in the absence of any drug, showed in their decay phase consistent deviations from an exponential time course, consisting of (a) "curvature," a progressive increase of decay rate during most of the decay phase, followed by (b) "late" tails. Both phenomena persisted when MEPCs (and channel lifetime) were prolonged by ethanol. Curvature was increased by muscle fiber depolarization and decreased by hyperpolarization. Receptor blockade by (+)-tubocurarine, alpha-bungarotoxin, hexamethonium, or myasthenic IgG accelerated the decay of the main part of MEPCs and eliminated curvature; the time constant of MEPCs became close to the channel time constant. We conclude that curvature arises from repeated action of ACh with cooperativity in ACh-receptor interaction; the voltage sensitivity of curvature follows from the voltage sensitivity of channel closing. Ethanol, in addition to its effect to prolong channel lifetime, enhances the tendency of ACh to act more than once to open channels before being lost to the system. Analysis of the rising phase of the MEPC, in terms of driving functions, also indicated that ethanol promotes channel opening by ACh; this action can account for a substantial increase of MEPC height by ethanol when MEPCs are made small by receptor blockade. Driving functions were also voltage sensitive, in a manner indicating acceleration of channel opening, but reduction of channel conductance, with hyperpolarization. Poisoning or inhibition of AChE prolonged MEPCs without altering the duration of ionic channels. Since ethanol caused further prolongation of MEPCs after poisoning of AChE, with little change in MEPC height, we conclude that the extension of mean channel lifetime by ethanol is accompanied by a similar extension of ACh binding to receptors. After poisoning of AChE, MEPCs became very variable in time course and the decay rate (tau-1) was correlated with MEPC height with a slope of log tau vs. log height of 0.77 for MEPCs of greater than 60% mean size. This slope is larger than expected from cooperativity in ACh-receptor interaction. Correlation of tau and height of MEPCs also exists when AChE is intact; the slope of log tau vs. log height was 0.12 with or without prolongation of MEPCs by ethanol.
J Gen Physiol 1984 Mar
PMID:The time course of miniature endplate currents and its modification by receptor blockade and ethanol. 632 90

Activities of choline acetyltransferase (CAT) and acetylcholinesterase (AChE) were measured in several regions of the spinal cord, spinal ganglia and the sciatic nerve following ligation of the abdominal aorta just below the renal arteries for 20; 40; 80 and 120 min. Aortic ligation for 40 min produced a significant increase in the activities of both enzymes in the lumbar spinal cord. After ligation lasting 80 min the activity of CAT dropped under the control level and that of AChE remained elevated and returned to the control level in animals sacrificed 120 after the ligation. Similar but smaller AChE elevation was also found in the lower thoracic and the sacral spinal cord, respectively. In ischemic spinal ganglia and the sciatic nerve a decrease in AChE activity was found.
Gen Physiol Biophys 1984 Jun
PMID:The dynamics of choline acetyltransferase and acetylcholinesterase changes in dog spinal cord during ischemia. 647 79

Sumithion is the most active cholinesterase inhibitor. The cholinesterase inhibiting action of the organophosphates (OPs) is better compensated by vitamin E in normal animals, but by vitamin A in vitamin A-deficient animals. The lipid peroxidation (LP) is enhanced by the antioxidant vitamins in the liver of normal rats; although they decrease it in the liver of vitamin A-deficient animals, in no case do they prevent the LP-enhancing effect of the OPs examined. The OPs examined inhibit protein synthesis in the liver of vitamin A-deficient animals.
Gen Pharmacol 1983
PMID:Some further data on the effects of two organophosphate pesticides on the oxidative metabolism in the liver. 666 50

An injection of 20 micrograms/l kg body wt of adrenaline, acetylcholine and histamine decreased AspAT and A1AT aminotransferase activity in blood plasma serum of 1 to 3-day-old Leghorn chicks. All hormones injected caused an increase in the activity of cholinesterase 1 min after injection.
Gen Pharmacol 1984
PMID:The effect of adrenaline, acetylcholine and histamine on aminotransferase A1AT and AspAT and cholinesterase activity in blood plasma of 1 to 3-day-old chicks. 669 84


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