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)

The binding of [3H]quinuclidinyl benzilate ([3H]QNB) to cardiac muscarinic receptors was inhibited not only by classical muscarinic antagonists but also by nicotinic blocking agents and inhibitors of acetylcholinesterase. Gallamine, pancuronium, ambenonium, and decamethonium were the most potent of these agents examined. All of the nicotinic antagonists with significant muscarinic receptor activity had two or three quaternary nitrogens, and the potency of a series of these compounds was a function of the distance between quaternary nitrogens. The effects of gallamine and pancuronium were studied in detail because these neuromuscular blocking agents showed heterogeneity in their binding to cardiac muscarinic receptors, whereas classical muscarinic antagonists such as QNB and atropine did not. Gallamine did not compete for all of the [3H]QNB binding sites on atrial membranes, but left at least 20% of [3H]QNB binding unaffected. Curves of pancuronium competition for [3H]QNB binding were shallow, consistent with two binding sites for pancuronium, with approximately 20% having low affinity. Additionally, in the presence of gallamine or pancuronium, [3H]QNB binding sites were no longer homogeneous, and Scatchard plots became nonlinear. Guanine nucleotides did not alter the effect of gallamine or pancuronium on [3H]QNB binding. Gallamine and pancuronium showed no agonist activity but, like atropine, completely antagonized muscarinic receptor-mediated inhibition of cyclic AMP formation. However, differences in the behavior of gallamine and atropine suggested that gallamine was not a purely competitive antagonist. Gallamine did not protect against receptor alkylation by propylbenzilylcholine mustard, and [3H]QNB dissociation was apparently slowed by gallamine. We interpret our data to suggest that gallamine not only competes for [3H]QNB binding sites, but also binds at a secondary site on the receptor, forming a ternary complex with [3H]QNB. Heterogeneity in ligand binding is proposed to result from the dual actions of gallamine and pancuronium as ligands at both primary and secondary sites on the cardiac muscarinic receptor.
Mol Pharmacol 1983 Jul
PMID:Heterogeneity of binding sites on cardiac muscarinic receptors induced by the neuromuscular blocking agents gallamine and pancuronium. 613 50

Superfusion of the organophosphorous acetylcholinesterase inhibitor soman (pinacolyl methylphosphonofluoridate; 0.01-25 microM) produced a dose-dependent reduction of extracellularly and intracellularly recorded synaptic responses in the isolated rat superior cervical ganglia at frequencies of orthodromic stimulation that do not normally produce synaptic depression. The magnitude of depression was dependent upon the frequency of stimulation (0.02-1 Hz), was maintained after the removal of soman from the superfusion solution, and recovered by over 65% during periods of inactivity. The depression of synaptic transmission produced by soman was not dependent upon the inhibition of acetylcholinesterase (AChE) activity by this agent. Transmission was increasingly depressed by doses of soman greater than those needed to inactivate all measurable ganglionic AChE activity. Dose-dependent depression of synaptic transmission in soman also occurred after pretreatment with the irreversible AChE inhibitor diisopropylphosphofluoridate (DFP; 100 microM), which inhibited greater than 98% of the AChE activity in the ganglia. Soman produced a decline in the input resistance, resting potential, spike amplitude, and spike threshold and a reduction in the hyperpolarizing afterpotential. Soman-induced depression of synaptic transmission was not due primarily to a blockade of postsynaptic nicotinic receptors. At concentrations of soman which produced significant depression in transmission, ganglionic depolarization produced by bath-applied carbamylcholine (carbachol) was either slightly depressed or facilitated. In the presence of soman, repetitive focal application of acetylcholine or carbachol did not reveal use-dependent desensitization. Muscarinic antagonists, atropine and pirenzepine, protected against the use-dependent depression of synaptic transmission induced by soman. These results suggest that a principal site of action for soman is at the presynaptic terminal and that this site is sensitive to muscarinic receptor blockade.
Cell Mol Neurobiol 1984 Dec
PMID:Noncholinesterase actions of an irreversible acetylcholinesterase inhibitor on synaptic transmission and membrane properties in autonomic ganglia. 615 5

Butyrylcholinesterase purified from human plasma and acetylcholinesterase purified from human red blood cells were used to immunize separate groups of BALB/c mice. A solid-phase immunoadsorbance assay was developed to screen and characterize antibodies specific for the cholinesterases. Immunized spleen cells were fused with a non-immunoglobulin-secreting myeloma cell line (FO). After two subcultures at limiting dilution, several clones secreting antibodies to acetylcholinesterase or butyrylcholinesterase were obtained. Selected clones were expanded as ascites tumors in immunosuppressed BALB/c mice. All tested immunoglobulins consisted of kappa light chains and either G1 or G2b heavy chains. Two-dimensional gel electrophoresis confirmed the monoclonal nature of each isolated antibody. None of the antibodies to acetylcholinesterase cross-reacted with butyrylcholinesterase, and vice versa. All tested antibodies exhibited high avidity for human enzyme, independent of the tissue source (apparent dissociation constants: 1-3 nM for acetylcholinesterase antibodies; 2-13 nM for butyrylcholinesterase antibodies). Treatment of enzymes with monoclonal antibodies increased the sedimentation coefficients (from 6.5 S to 12 S for acetylcholinesterase, from 11 S to 18 S or 20 S for butyrylcholinesterase). All of the monoclonal antibodies displayed marked species specificity. Several antibodies reacted only with human enzyme; others reacted with enzyme from nonhuman primates as well. A few of the butyrylcholinesterase antibodies cross-reacted weakly with enzyme from dog, cat, and horse, but none reacted with the enzyme from rat, guinea pig, and chicken. One acetylcholinesterase antibody cross-reacted with acetylcholinesterase of rabbit and guinea pig. The avidity, species selectivity, and other properties of these antibody reagents will be useful in future studies on the regulation and disposition of cholinesterases.
Mol Pharmacol 1983 Nov
PMID:Production and characterization of separate monoclonal antibodies to human acetylcholinesterase and butyrylcholinesterase. 619 17

We have used a set of overlapping cloned segments defining a 315 kb (X 10(3) base-pairs) region of Drosophila melanogaster chromosomal DNA to map the sequences associated with the polytene band-interbands (chromomeric units) and with the lethal complementation groups contained within this region. The molecular map positions of the 13 +/- 1 chromomeric units from the 87D5-6 to 87E5, 6 region of the third chromosome were determined by in situ hybridization of selected segments to the polytene chromosomes. The length of the largest chromomeric unit within the 315 kb region is approximately 160 kb, while that for the smallest is less than 7 kb and may be as short as 3 kb. By mapping the breakpoints of deletions within the 315 kb region, we have located its 12 lethal complementation groups, which include the genes coding for acetylcholinesterase (Ace) and xanthine dehydrogenase (rosy). Comparison of the two molecular maps indicates a one-to-one topographical correlation between the genetic and chromomeric units.
J Mol Biol 1983 Jul 25
PMID:Molecular mapping of genetic and chromomeric units in Drosophila melanogaster. 622 22

By measuring the permeability across the lipid bilayer in the presence and absence of membrane-bound protein or glycoprotein it should be possible to get an impression concerning their ability to penetrate into the membrane bilayer. Proteins such as phospholipase A2 and acetylcholinesterase markedly increase the permeability in contrast to glycoproteins (ovomucoid and orosomucoid) and cytochrome C. The results may serve as an indication of the type of interaction between lipids and membrane components.
Mol Biol Rep 1982 Apr 16
PMID:Glycoprotein and protein induced changes in liposome permeability. 628 80

The actions of pyridostigmine (Pyr), an anticholinesterase agent, were studied on the acetylcholine (ACh) receptor-ion channel complex and on the electrically excitable membrane of the frog cutaneous pectoris and sartorius muscles and the chronically denervated soleus muscle of the rat. Pyr at concentrations of 0.2-0.4 mM potentiated the indirect evoked muscle twitch and at concentrations greater than or equal to 0.8 mM depressed the indirect twitch with an IC50 of about 2 mM. Twitch depression produced by Pyr was reversed slowly, and after a 60-min wash only 59% of the control muscle twitch had returned. Pyr did not affect either the membrane potential or the muscle action potential. Pyr had several effects at the neuromuscular junction of the frog and rat. It decreased the peak amplitude of the end-plate current (EPC) in a voltage- and concentration-dependent manner. In contrast to diisopropylfluorophosphate, which depresses the EPC amplitude and induces a double exponential decay of the EPC and miniature end-plate current (MEPC), Pyr produced a marked prolongation of the time constants of EPC and MEPC decay while maintaining a single exponential decay. The decrease caused by Pyr of indirect twitch tension, EPC amplitude, and ACh sensitivity indicates mechanisms which limit the number and/or properties of conducting channels. The drug decreased channel conductance and prolonged channel lifetime as revealed by Fourier analysis of ACh-induced end-plate current fluctuations. An altered form of the conducting species induced by Pyr appears to be responsible for either the apparent agonist-induced depolarization or its ability to increase the affinity of ACh for its recognition site. Pyr was also found to inhibit the binding of ACh and alpha-bungarotoxin to receptor-rich membrane from the electric organ of Torpedo nobiliana, and to have a higher affinity for the receptor than for the ion channel binding sites. These actions are distinct from acetylcholinesterase inhibition caused by the agent. Strong evidence suggests that the direct influences of the agent on neuromuscular transmission involve at least three distinct, although possibly interacting, mechanisms: (a) a weak agonist action, (b) the formation of desensitized receptor-complex intermediates, and (c) the alteration of the conductance properties of active channels.
Mol Pharmacol 1984 Jan
PMID:The nature of the interactions of pyridostigmine with the nicotinic acetylcholine receptor-ionic channel complex. I. Agonist, desensitizing, and binding properties. 632 55

Choline, acetylcholine and betaine used as a sole carbon source, effectuate in Ps. aeruginosa an acid phosphatase activity in addition to a cholinesterase activity. Induction of both enzyme activities was repressed by succinate or glucose. Cyclic AMP failed to relieve the repression produced by these compounds. Substrates not related to choline and used as a sole source of carbon, were inefficient to produce induction of both enzymes. The in-vitro action of choline, acetylcholine and betaine on Ps. aeruginosa acid phosphatase and cholinesterase has also been studied. To perform these studies periplasmic extracts obtained by EDTA-lysozyme treatment of the cells grown on choline or betaine as sole source of carbon, were used. Acid phosphatase activity was competitively inhibited by betaine, whereas the inhibition produced by choline and acetylcholine showed competitive and noncompetitive components. Cholinesterase activity was noncompetitively inhibited by betaine. At low acetylthiocholine concentration choline was an inhibitor of cholinesterase, whereas at high substrate concentration choline raised the hydrolysis rate of acetylthiocholine. These findings allow the conclusion that acid phosphatase and cholinesterase are specifically induced by choline and its metabolites derivatives. Kinetic results led us to postulate that acid phosphatase and cholinesterase contain a similar allosteric site. This site would either be of an anionic nature or show affinity to a methyl group or display both characteristics.
Mol Cell Biochem 1983
PMID:Induction of acid phosphatase and cholinesterase activities in Ps. aeruginosa and their in-vitro control by choline, acetylcholine and betaine. 640 29

A chromosomal walk is described that covers 315 X 10(3) base-pairs of DNA from the 87DE region of the third chromosome of Drosophila melanogaster. The walk includes the DNA for the rosy and Ace loci, which code for xanthine dehydrogenase and acetylcholinesterase, respectively. Several dispersed repetitive elements were encountered in the walk. In every case, their positions in the chromosome differed in different strains, and so they are all presumed to be transposable elements. Several rearrangement breakpoints have been localized within the walk, including the break for In(3R) Cbx+R1 (87E1, 2-89E1, 2). One breakpoint fusion fragment of this inversion was isolated to jump from 87E into the cluster of homeotic genes of the bithorax complex, at 89E1-4.
J Mol Biol 1983 Jul 25
PMID:Chromosomal walking and jumping to isolate DNA from the Ace and rosy loci and the bithorax complex in Drosophila melanogaster. 641 77

Different compounds derived from choline, and obtained by demethylation or by oxidation of the primary alcohol group with subsequent N-demethylation, were tested as inducer agents of acid phosphatase and cholinesterase in Ps. aeruginosa. It was found that betaine and dimethylglycine were the most effective inducers of both enzyme activities. These metabolites including choline itself, were not inducers of acid phosphatase and cholinesterase in other Gram-negative bacteria such as: Escherichia coli, Salmonella typhimurium, Shigella flexneri, Enterobacter liquefacciens and Proteus mirabilis. The acid phosphatase activities found in these bacteria were not inhibited in vitro by choline, betaine and phosphorylcholine. From these results it may be concluded that the acid phosphatase activity from Ps. aeruginosa is different from the same activity observed in the other bacteria. In addition, it is also shown that Ps. aeruginosa acid phosphatase and cholinesterase were inhibited by a number of compounds containing a positively charged amino group, with methyl or ethyl groups bound to it. These results seem to confirm that Ps. aeruginosa acid phosphatase and cholinesterase may contain a similar anionic site.
Mol Cell Biochem 1984 Sep
PMID:Pseudomonas aeruginosa acid phosphatase and cholinesterase induced by choline and its metabolic derivatives may contain a similar anionic peripheral site. 643 82

An ultrastructural, histochemical, and biochemical study of the electric organ of the South American Torpedinid ray, Discopyge tschudii, was carried out. Fine structural cytochemical localization of acetylcholinesterase (AChE) indicated that most of the esterase was associated with the basal lamina. Electron microscopy indicated no marked differences in the electrocyte ultrastructure between Discopyge and Torpedo californica. Discopyge electric organ possessed three molecular forms, two asymmetric forms (16 S and 13 S) and one globular hydrophobic form (6.5 S). The asymmetric 16 S AChE form was solubilized by heparin, a sulfated glycosaminoglycan, suggesting that heparin-like macromolecules are involved in the binding of the enzyme to the basal lamina. Our results show that cell-free translated AChE peptides, synthesized using Discopyge electric organ poly(A+) RNA, correspond to a main band of 62,000 daltons which probably represents the catalytic subunit of the asymmetric AChE.
Cell Mol Neurobiol 1984 Jun
PMID:The electric organ of Discopyge tschudii: its innervated face and the biology of acetylcholinesterase. 648 42


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