Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brugia malayi, a lymphatic filarial parasite, secretes acetylcholinesterase during in vitro cultivation. A significant amount of enzyme activity was detected both in culture media and somatic extracts of adult and microfilarial stages of the parasite. The microfilarial stage produces three times more enzyme than adult parasites as a proportion of total protein. The enzyme has true acetylcholinesterase (AChE) activity as hydrolysis of acetylthiocholine is three times faster than butyrylthiocholine and is inhibited by eserine, a specific inhibitor of AChE. Secretory enzyme from adult female parasite excretory-secretory material (ES) was enriched 23 fold using copper chelating and concanavalin A (Con A) affinity chromatography. The Con A eluate showed a major protein band of 100 kDa and a minor 200 kDa component. The ES enzyme is antigenic and cross reacts with antibodies raised in mice against AChE from electric eel by enzyme-linked immunosorbent assay and immunoprecipitation. Immunoprecipitation of 125I-labelled microfilarial ES and adult ES with anti-electric eel AChE antibodies revealed three proteins of 30, 40 and 200 kDa in microfilariae and two proteins of 100 and 200 kDa in adult female ES. It appears that filarial secretory AChE exists in multiple molecular forms.
Mol Biochem Parasitol 1987 Dec
PMID:Secretory acetylcholinesterases from Brugia malayi adult and microfilarial parasites. 312 28

Two enzymes, alkaline phosphatase and acetylcholinesterase (AChE), have been shown previously to be components of the surface of the trematode parasite Schistosoma mansoni. In this study we report that both these enzymes and other serine hydrolases are susceptible to release from the S. mansoni tegumental membrane by a phosphatidylinositol-specific phospholipase C (PIPLC) of bacterial origin. These data suggest that AChE and alkaline phosphatase of S. mansoni, as in higher organisms, are anchored to the membrane via covalently attached phosphatidylinositol. The release of AChE from the vesicular fraction of the parasite with PIPLC occurs in a concentration-dependent manner. Sucrose gradient centrifugation of the PIPLC-released AChE showed a single 8.3 S molecular form, similar to that observed for AChE solubilized by Triton X-100. PIPLC removed large amounts of AChE from the surface of intact schistosomula in culture, with no impairment of the viability of the parasite. In this case, an increase in the overall levels of AChE in the intact parasite was observed after addition of PIPLC.
Mol Biochem Parasitol 1988 Jun
PMID:Acetylcholinesterase in Schistosoma mansoni is anchored to the membrane via covalently attached phosphatidylinositol. 313 66

Globular forms (G forms) of acetylcholinesterase (AChE) are formed by monomers, dimers and tetramers of the catalytic subunits (G1, G2 and G4). In this work the hydrophobic G2 and G4 AChE forms were purified to homogeneity from Discopyge electric organ and bovine caudate nucleus and studied from different points of view, including: velocity sedimentation, affinity to lectins and SDS-polyacrylamide gel electrophoresis under reducing and non-reducing conditions. The polypeptide composition of Discopyge electric organ G2 is similar to Torpedo, however the pattern of the brain G4 AChE is much complex. Under non-reducing conditions the catalytic subunit possesses a molecular weight of 65 kDa, however this value increases to 68 kDa after reduction, suggesting that intrachain-disulfide bonds are important in the folding of the catalytic subunits of the AChE. Also it was found that after mild proteolysis; the (125I)-TID-20 kDa fragment decreased its molecular weight to approximately 10 kDa with little loss of AChE activity. Finally, we suggest a model for the organization of the different domains of the hydrophobic anchor fragment of the G4 form.
Mol Cell Biochem 1988 May
PMID:Characterization of a tetrameric G4 form of acetylcholinesterase from bovine brain: a comparison with the dimeric G2 form of the electric organ. 317 45

The cholinergic agonists acetylcholine (ACh), carbamylcholine and methacholine were found to be equieffective in reducing the force of left atrial contraction, but to differ in their ability to shorten the action potential duration. The irreversible cholinesterase inhibitor soman had no effect on the actions of the non-hydrolyzable agonist carbamylcholine, but potentiated the actions of ACh. The reversible inhibitor edrophonium both potentiated and antagonized the effects of ACh. It antagonized the effects of carbamylcholine and after atrial cholinesterase was inhibited with soman it also antagonized the effects of ACh. Its anticholinesterase action and inhibitory action at the muscarinic receptor were confirmed in separate studies. Edrophonium is approximately 12 times more potent as an anticholinesterase than it is in blocking the muscarinic receptor. However, some actions of edrophonium cannot be explained in the context of its anticholinergic and antiesterase actions. Thus it increases the force of atrial contraction and antagonizes the negative inotropy due to soman. An inhibitory effect on an outward K+ current may be involved. The difference in the ability of the three cholinergic agonists to shorten the action potential may also be related to differences in efficacy at this K+ channel.
J Mol Cell Cardiol 1986 Mar
PMID:Modification of the effects of muscarinic agonists by reversible and irreversible anticholinesterase compounds in the guinea pig atrium. 351 25

The responsiveness of Aplysia acetylcholine receptors (AChR) was studied using a polyene antibiotic, filipin, which specifically complexes cholesterol, and another compound, chlorpromazine (CPZ), which inserts at the proteolipidic interface. Both substances enhanced the evoked postsynaptic responses or responses to iontophoretic application of carbachol only on the H-type receptor (opening a Cl-permeability), whereas at the same concentrations filipin was without effect on the D-type receptor (opening a cationic permeability) while CPZ depressed the D-type response. The facilitation observed specifically for the H-type receptor was similar to that previously described after acetylcholinesterase (AChE) inhibition or when low concentrations of detergents were applied to this preparation. No additive effect was obtained after the addition of chlorpromazine following a maximal potentiation obtained with an anticholinesterase agent. Since at Aplysia central neurons, AChE is a membranal protein, we propose that the facilitation of H-type responses is attributable to the removal of a modulatory action of AChE on AChR. Filipin or chlorpromazine might disrupt the interaction between AChR and AChE.
Cell Mol Neurobiol 1987 Mar
PMID:Modulation of an acetylcholine receptor responsiveness by filipin and chlorpromazine studied in neurons of Aplysia californica. 359 17

Vibrational Raman spectroscopy has been used to study the conformation of the 11 S form of acetylcholinesterase from Torpedo californica. Secondary structure analysis by the method of Williams [(1983) J. Mol. Biol. 166, 581-603] shows 49% alpha-helical structure, 23% beta-sheets, 11% turns and 15% undefined structure. Secondary structure estimates obtained for this enzyme by Raman spectroscopy and circular dichroism have been analyzed.
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PMID:Raman spectroscopic study on the conformation of 11 S form acetylcholinesterase from Torpedo californica. 359 73

The synthesis of decidium and hexidium diiodides, their spectroscopic properties, and association with acetylcholinesterase from Torpedo californica are described and compared with those for propidium. Decidium, hexidium, and propidium, bisquaternary analogs of the fluorescent phenanthridinium ligand ethidium, contain 10, 6, and 3 methylene carbons, respectively, interposed between the exocyclic and endocyclic quaternary nitrogens. The three ligands exhibit linear competitive inhibition of enzyme carbamylation by N-methyl-7-dimethylcarbamoxyquinolinium. Dissociation constants for decidium, hexidium, and propidium are found by direct fluorescence titration to be 2.1 +/- 0.2 X 10(-8), 5.8 +/- 1.4 X 10(-7), and 3.7 +/- 0.4 X 10(-6) M, values in close accord with the inhibition constants obtained from kinetic analyses. Association of the three ligands is characterized by a stoichiometry of one fluorescent ligand per 80-kDa molecular weight subunit and occurs with respective 6.5-, 4.5-, and 3-fold increases in both quantum yield and fluorescence lifetime. Decidium and hexidium, in marked contrast with propidium, are dissociated by ligands selective for the active center and undergo pronounced reduction in affinity upon modification of the active center with pyrenebutyl methylphosphonofluoridate. Whereas the kinetics reveal no clear distinctions in inhibitory action of the three ligands, the fluorescence studies indicate that the alkyltrimethylammonium moiety of decidium and hexidium occludes the active center; propidium, in contrast, associates solely with the peripheral anionic site and does not occlude the active center. The temperature dependence of binding indicates that decidium association engenders a substantial increase (+55 eu) in entropy. The data indicate that the active center and peripheral anionic sites are separated by a crevice which can accommodate the hydrocarbon portion of extended n-alkyl cationic ligands, thereby affording entropic stabilization of complex formation. This stabilization is realized, however, only when the anionic subsite of the active center is not occluded, enabling electrostatic interaction between cationic ligand and the anionic active center.
Mol Pharmacol 1987 Jun
PMID:Site selectivity of fluorescent bisquaternary phenanthridinium ligands for acetylcholinesterase. 360 Jun 5

The distribution of sympathetic nerve fibers in the regions of the bundle branches of bovine and rat hearts was examined by the glyoxylic acid-induced method for histofluorescence demonstration of catecholamines and by acetylcholinesterase (AChE) histochemistry. The studies on the bovine heart were concentrated on the nerve fascicles, the arteries and the ganglionic cells, and showed that (1) the AChE-positive nerve fascicles that occur just outside the bundle branches show a positive catecholamine-fluorescence reaction to varying degrees, the paraarterial nerve fascicles showing a uniform reaction; (2) the AChE-positive nerve fascicles within the bundle branches contain a few, mainly varicose, sympathetic nerve fibers; (3) extensive plexuses of sympathetic nerve fibers supply the arterial branches; and (4) sympathetic nerve fibers occur close to some of the ganglionic cells. The pattern of distribution of sympathetic nerve fibers in the region of the SA node was found to be essentially the same. The studies on the rat heart showed that (1) the septal arteries that occur in the proximity of the bundle branches are accompanied by the sympathetic component of innervation; and (2) there is a substantial number of varicose sympathetic nerve fibers within the bundle branches. These observations show that there is a pronounced sympathetic innervation in bundle branch regions and suggest that the paraarterial route is the most important for sympathetic nerve fibers to reach these regions.
J Mol Cell Cardiol 1987 Jun
PMID:Marked sympathetic innervation in the regions of the bundle branches shown by catecholamine histofluorescence. 362 85

1. Miniature postsynaptic currents were analyzed at an inhibitory cholinergic neuroneuronal synapse in the buccal ganglion of Aplysia. Under double voltage-clamp, it was possible to induce postsynaptic currents by long-duration depolarizations of the presynaptic neuron and to analyze these as the linear summation of individual miniature postsynaptic currents (MPSCs). The amplitude of these miniature currents (imin) was calculated from the ratio of the variance of the noise (E2) to the mean of the postsynaptic current (Im), according to Campbell's theorem, with imin = 2E2/Im. Their decay time (tau min) was obtained from the cutoff frequencies of the power spectra obtained from the noise. 2. Neither the conductance nor the decay time of MPSCs was voltage dependent. However, imin appeared to decrease when the quantal content of the response increased. Meanwhile, tau min increased slightly with Imin. 3. Carbamylcholine was injected into the neuropile and this led to a decrease in imin and a slight increase in tau min. 4. Power spectra obtained after the application of inhibitors of acetylcholinesterase (AChE), with or without curare, suggested that acetylcholine (ACh) does not accumulate during large depolarizations. 5. The possible origin of the nonlinear relationship between the variance and the mean of the postsynaptic currents is discussed.
Cell Mol Neurobiol 1987 Jun
PMID:Properties of miniature postsynaptic currents during depolarization-induced release at a cholinergic neuroneuronal synapse. 365 14

The benzomorphan opiate, (-)N-allynormetazocine [(-)ANMC, (-)SKF10047], has been shown previously to bind two distinct sites on acetylcholine receptor (AChR)-rich membranes from Torpedo electroplaque. The low affinity site seems to correspond to the site for noncompetitive blockers on the AChR. The high affinity site, which can be photoaffinity labeled using UV irradiation, was distinct from this site. We show here, using a variety of techniques, that the high affinity binding site for (-)ANMC is on the acetylcholinesterase (AChE) associated with these membranes. The Triton X-100-solubilized peptide photolabeled with (-)[3H]ANMC co-migrates with acetylcholinesterase activity on velocity sucrose gradient centrifugation and fast protein liquid chromatography. In addition, the labeled peptide cannot be precipitated with monoclonal or polyclonal antibodies raised against the nicotinic AChR but can be precipitated with anti-AChE antibodies. Localization of the binding site on AChE was confirmed by photolabeling of and reversible binding to the 11 S AChE purified from Torpedo californica. The binding and photolabeling had characteristics and affinity similar to those for the high affinity binding site in Torpedo electroplaque membranes. Competition studies with specific AChE inhibitors suggest that the binding site may be the catalytic site of the enzyme, which exists on the 66-kDa globular protein. The effect of (-) and (+)ANMC on AChE activity was also investigated. ANMC inhibited AChE activity at micromolar concentrations in a stereoselective fashion, with the (-)isomer exhibiting a 2-fold higher affinity than the (+) isomer. The inhibition was consistent with a competitive blockade of AChE activity.
Mol Pharmacol 1987 Oct
PMID:Interaction of a benzomorphan opiate with acetylcholinesterase and the nicotinic acetylcholine receptor. 367 Feb 80


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