Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.8 (cholinesterase)
12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rates of regeneration of acetylcholinesterase (AChE) and propionylcholinesterase (PrChE) in the supernatants of aqueous homogenates of rat superior cervical ganglia, centrifuged at 100,000 g for 90 min, were determined at 1, 3, 6, and 16 h following their inactivation (greater than 90%) by administration of sarin, 2.0 mumol/kg i.v. Values were compared with those in animals in which the PrChE was continually suppressed by the repeated, fractional administration of iso-OMPA, in a total dose of 10 or 20 mumol/kg i.p. These doses of iso-OMPA alone produced 96-99% inactivation of PrChE with no detectable effect on AChE. Significant suppression of AChE regeneration by iso-OMPA administration was noted only at 6 h; in contrast with earlier findings in the cat, administration of iso-OMPA alone caused no significant increase in ganglionic AChE activity.
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PMID:Effects of selective alkylphosphorylation of propionylcholinesterase on the regeneration of acetylcholinesterase in the aqueous soluble fraction of superior cervical ganglia of the rat following sarin. 746 67

Serum pseudocholinesterase (PChE) was discovered in 1932. Since this protein mimics many of the catalytic properties of acetylcholinesterase, it has traditionally been referred to as PChE, even though its true biological function is unknown. Serum PChE is synthesized in the liver and secreted into the circulation as a sialated glycoprotein. Although no convincing evidence of biological function exists, a significant number of obese and diabetic patients have elevated levels of PChE. The same phenomenon is found in experimental animal models of obesity, diabetes and hyperlipoproteinemia. Streptozotocin-induced diabetic mice showed increased serum PChE activity concomitant with increased serum triacylglycerol and PChE activity declined with treatment. Iso-OMPA, a nontoxic inhibitor of serum PChE, reduced serum and liver triacylglycerols and serum VLDL in streptozotocin-induced rodent diabetes. These findings suggest that PChE may have a role in VLDL metabolism.
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PMID:Serum pseudocholinesterase and very-low-density lipoprotein metabolism. 793 19

During chicken neurogenesis, the sequential expression of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) between final cell proliferation and differentiation is functionally not understood. Recently, cholinesterases have been shown to regulate neurite growth in vitro. Here, we investigated the effects of inhibition of BChE on laminar histogenesis in retinospheroids that arise from dissociated embryonic chicken retinal cells in rotation culture. In the presence of the BChE inhibitor iso-OMPA (tetraisopropyl pyrophosphoramide), the number of spheroids/dish is increased, and their diameter is decreased by about 20%, corresponding to about 50% volume size. As a corollary, the course of histotypical differentiation is dramatically accelerated. Thus as a consequence of BChE inhibition both, organization of nuclear cell layers and of plexiform-like (neuropile) areas, as detected by an antibody to the fiber fasciculation protein F11, is temporally advanced by at least two days. Moreover, AChE is almost fully diminished in these areas. The results further demonstrate novel roles of cholinesterases during laminar histogenesis of coherent neural networks in vitro.
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PMID:Butyrylcholinesterase regulates laminar retinogenesis of the chick embryo in vitro. 795 7

The occurrence of cholinesterases has been demonstrated in retinas of several mammalian species. Histochemical staining techniques indicate that the acetylcholinesterases (AChE) are present in amacrine cells and their neighboring bipolar cells. However, the nature of retinal cholinesterases and their interactions with specific cholinesterase inhibitors are not known. Therefore, we have studied the inhibition of the rat retinal cholinesterase activity by BW284C51, a selective inhibitor of AChE, and iso-OMPA, a selective inhibitor of butyrylcholinesterase (BChE). Retinas from Zivic-Miller rats were solubilized by sonication in phosphate buffer (0.134 M, pH 7.2) at 4 degrees C for 20 min. The cholinesterase activity in the sonicate was determined by a radiometric method using 14C-acetylcholine (ACh) as substrate (10(-2) M). Excess 14C-ACh was adsorbed by Amberlite CG-120 cation exchange resin. 14C-acetate formed and retained in the aqueous medium was determined by liquid scintillation counting. This study gave the following results: (a) Rat retinal sonicate gave total cholinesterase activity of 3.76 mumol of ACh hydrolyzed/mg protein/15 min; (b) This activity was inhibited by BW284C51 (IC50, 0.115 microM). Iso-OMPA (IC50, 500 microM) did not cause significant inhibition at 0.115 microM. These observations suggest that the rat retinal cholinesterase is predominantly AChE.
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PMID:Nature of cholinesterase in the rat retina. 820 26

In search of the molecular mechanisms underlying the broad substrate and inhibitor specificities of butyrylcholinesterase (BuChE), we employed site-directed mutagenesis to modify the catalytic triad residue Ser198, the acyl pocket Leu286 and adjacent Phe329 residues, and Met437 and Tyr440 located near the choline binding site. Mutant proteins were produced in microinjected Xenopus oocytes, and Km values towards butyrylthiocholine and IC50 values for the organophosphates diisopropylfluorophosphonate (DFP), diethoxyphosphinylthiocholine iodide (echothiophate), and tetraisopropylpyrophosphoramide (iso-OMPA) were determined. Substitution of Ser198 by cysteine and Met437 by aspartate nearly abolished activity, and other mutations of Ser198 completely abolished it. Tyr440 and Leu286 mutants remained active, but with higher Km and IC50 values. Rates of inhibition by DFP were roughly parallel to IC50 values for several Leu286 mutants. Both Km and IC50 values increased for Leu286 mutants in the order Asp < Gln < Lys. In contrast, cysteine, leucine, and glutamine mutants of Phe329 displayed unmodified Km values toward butyrylthiocholine, but up to 10-fold decreased IC50 values for DFP, iso-OMPA, and echothiophate. These findings add Tyr440 and Phe329 to the list of residues interacting with substrate and ligands, demonstrate plasticity in the active site region of BuChE, and foreshadow the design of recombinant BuChEs with tailored scavenging properties.
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PMID:Site-directed mutagenesis of active site residues reveals plasticity of human butyrylcholinesterase in substrate and inhibitor interactions. 829 37

Cholinesterase activity is detectable in the Japanese quail embryo, in the yolk and subembryonic liquid, but not in the albumen. Obviously, this enzyme is deposited by the hen into the yolk and from there it is transferred to the subembryonic liquid. In contrast, in the embryo the enzyme is synthesized by itself and the amount increases with the age of the embryo. By using BW284c51 1,5-bis-(4-allyldimethylammoniumphenyl)pentan-3-one bromide and ISO-OMPA tetraisoprophylpyrophosphoramide as inhibitors, it was found that the enzyme in the embryo is predominantly acetylcholinesterase (EC 3.1.1.7), whereas that in the yolk and subembryonic liquid is butyrylcholinesterase (EC 3.1.1.8). Both types are inhibited by dichlorphos. However, the embryonic enzyme activity is restored within 8 hr, whereas that in the subembryonic liquid remained inactive at least for 72 hr after inhibition. Enzyme inhibition leads to retardation of the development, to reduced accumulation of glucose and amino acids in the subembryonic liquid and finally to death of the embryo, suggesting that the developmental retardation is due to the restricted supply of glucose and amino acids. Surprisingly, most of the embryos die when the embryonic enzyme activity has again been restored.
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PMID:Activity of cholinesterases in the Japanese quail embryo. Effects of dichlorphos on the embryonic development. 842 27

1. Neostigmine and BW284C51 induced concentration-dependent contractions in human isolated bronchial preparations whereas tetraisopropylpyrophosphoramide (iso-OMPA) was inactive on airway resting tone. 2. Neostigmine (0.1 microM) or iso-OMPA (100 microM) increased acetylcholine sensitivity in human isolated bronchial preparations but did not alter methacholine or carbachol concentration-effect curves. 3. In the presence of iso-OMPA (10 microM) the bronchial rings were more sensitive to neostigmine. The pD2 values were, control: 6.05 +/- 0.15 and treated: 6.91 +/- 0.14. 4. Neostigmine or iso-OMPA retarded the degradation of acetylcholine when this substrate was exogenously added to human isolated airways. A marked reduction of acetylcholine degradation was observed in the presence of both inhibitors. Exogenous butyrylcholine degradation was prevented by iso-OMPA (10 microM) but not by neostigmine (0.1 microM). 5. These results suggest the presence of butyrylcholinesterase activity in human bronchial muscle and this enzyme may co-regulate the degradation of acetylcholine in this tissue.
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PMID:Degradation of acetylcholine in human airways: role of butyrylcholinesterase. 848 30

The occurrence of cholinesterases (ChE) has been demonstrated in retinas of several mammalian species. Using BW284C51 and iso-OMPA as selective inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively, it has been demonstrated that the rat retinal ChE is predominantly AChE. Therefore the kinetic nature of inhibition of the rat retinal AChE by BW284C51 was studied using acetyl-6-methylthiocholine (AMTCh) as a selective substrate of AChE. AChE activity of the rat retinal sonicates was assayed using AMTCh as the substrate in the presence of 5,5-dithiobis-2-nitrobenzoate and yellow 5-thio-2-nitrobenzoic anion was measured by the absorption at 412 millimicrons using a spectrophotometer. The substrate (AMTCh) was varied between 0.1 and 0.5 mM. The inhibitor concentrations used were 2.1 and 4.2 nM. Double-reciprocal plots between substrate concentrations and the velocities for the enzymatic hydrolysis of AMTCh in the presence and absence of inhibitor were constructed. This study gave the following results: BW284C51 was a potent inhibitor of the hydrolysis of AMTCh by rat retinal AChE (IC50, 5.2 nM). The nature of the inhibition was found to be competitive as the double reciprocal plots with and without the inhibitor crossed on the ordinate.
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PMID:Evaluation of the nature of rat retinal acetylcholinesterase using a specific substrate and a specific inhibitor. 859 Feb 72

The distribution of acetylcholinesterase activity in human Meibomian glands was evaluated using enzyme-histochemical methods. The butyrylcholinesterase (BuChE) inhibitor, tetraisopropyl pyrophosphoramide (iso-OMPA), was used to localize acetylcholinesterase (AChE) activity, the AChE inhibitor, 1,5-bis (4-allyldimethylammoniumphenyl) pentan-3-one dibromide (BW284c51), was used to localize BuChE activity, and eserine was used to inhibit all cholinesterase activity in control incubations; the appropriate specific inhibitors for competing enzymic activities were added to the incubation medium. At the light microscopic level, acetylcholinesterase reaction product appeared as cytoplasmic brown deposits, often crystalline. A very dense accumulation of AChE-positive nerve fibers was seen in the form of a network around the acinar and the ductal tissue of the glands. No discrete nerve endings were observed, whereas a strong reaction was elicited in some fibers in close association with blood vessels. These observations suggest that the cholinergic system is involved in the regulation of the Meibomian glands secretory function.
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PMID:Histochemical demonstration of acetylcholinesterase activity in human Meibomian glands. 874 Oct 98

1. Human isolated pulmonary vessels were treated with cholinesterase (ChE) inhibitors to determine the role of these enzymes in regulating vascular muscle tone. In addition, kinetic parameters were determined for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in human pulmonary vessel homogenates. 2. Carbachol (CCh) and acetylcholine (ACh) were equipotent contractile agonists in human pulmonary arteries (pD2 values, 5.28 +/- 0.05 and 5.65 +/- 0.16; Emax, 0.91 +/- 0.26 and 0.98 +/- 0.30 g wt. for CCh and ACh, respectively; n = 7). In venous preparations, ACh was ineffective and CCh induced small contractions (Emax, 0.08 +/- 0.04 g wt; n = 13). 3. In human pulmonary arteries following pretreatment with tetraisopropylpyrophosphoramide (iso-OMPA, 100 microM), an increased sensitivity to the contractile agonist ACh was observed (pD2 values, 5.80 +/- 0.13 and 6.37 +/- 0.19 for control and treated preparations, respectively; n = 5). This pretreatment had no effect on the CCh concentration response curve. In contrast, human pulmonary veins pretreated with iso-OMPA failed to elicit a contractile response to ACh. 4. Neither Iso-OMPA nor neostigmine elicited concentration-dependent contractions in human isolated pulmonary arteries or veins. These results suggest the absence of sufficient spontaneous release of ACh to modulate human pulmonary vessel basal tone. 5. CCh was less potent than ACh in relaxing precontracted human isolated pulmonary arteries (pD2 value, CCh: 6.55 +/- 0.15 and ACh: 7.16 +/- 0.13, n = 4) and veins (pD2 value, CCh: 4.95 +/- 0.13; n = 5 and ACh: 5.56 +/- 0.17; n = 6). Pretreatment of vessels with either iso-OMPA or neostigmine did not modify ACh relaxant responses in either type of preparation. 6. In human pulmonary veins, the ChE activity was two fold greater than in arteries (n = 6). Vmax for AChE was 1.73 +/- 0.24 and 3.36 +/- 0.26 miu mg-1 protein in arteries and veins, respectively, whereas Vss for BChE was 1.83 +/- 0.22 and 4.71 +/- 0.17 miu mg-1 protein, in these respectively. 7. In human pulmonary arteries, BChE activity may play a role in the smooth muscle contraction but not on the smooth muscle endothelium-dependent relaxation induced by ACh. A role for ChE activity in the control of venous tone is presently difficult to observe, even though this tissue contains a greater amount of enzyme than the artery.
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PMID:Cholinesterase activity in human pulmonary arteries and veins. 922 57


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