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)

A membrane vesicle preparation was used to examine characteristics of the human placental cholinergic system. Plasma membrane vesicles were prepared from the microvillous surface of the human placental syncytiotrophoblast. Membranes were purified 18 -to 20-fold as indicated by 5'-nucleotidase activity. Vesicle cholinesterase activity was enriched and had a substrate preference consistent with that of acetylcholinesterase (acetylcholine greater than acetyl-beta-methylcholine greater than butyryl-choline). Choline acetyltransferase specific activity was reduced 80%. The synthetic muscarinic ligand, [3H]-quinuclidinyl benzilate (QNB), was used to identify two classes of muscarinic cholinergic binding sites. The dissociation constant of QNB binding was 80 pM and 30 nM for the two sites. The sites were saturable and bound 9 fmoles and 910 fmoles per mg protein for the high and low affinity sites, respectively. Specific binding was inhibited by scopolamine, atropine, carbamylcholine (CCH), and diphenhydramine, but not by non-muscarinic ligands-i.e. GABA, glycine, d-amphetamine, kappa-bungarotoxin and nicotine. The cholinergic agonist CCh had no effect on active AIB transport, although pharmacologic doses (lmM) of atropine, scopolamine and lidocaine reduced Na-gradient active transport of kappa-aminoisobutyric acid (AIB). No effect on Na-independent AIB transport was observed. Thus, these drugs apparently reduced AIB uptake through their shared local anesthetic activity and not through a central cholinergic mechanism. In contrast, CCh was able to stimulate Ca2+ uptake by the vesicles in a dose-dependent manner paralleling its ability to inhibit QNB binding. The CCh-stimulated Ca2+ uptake was inhibited by scopolamine, implying its mediation via cholinergic-type binding sites. The membrane vesicle preparation therefore provides a useful model for examination of the role of the human placental cholinergic system.
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PMID:Syncytiotrophoblast membrane vesicles: a model for examining the human placental cholinergic system. 733 61

Gamma aminobutyric acid injected into the lateral brain ventricle of white rats in doses of 0.6, 0.8 and 1.6 mg raised the level of acetylcholine and in doses of 0.2, 0.4, 0.6, 0.8 and 1.6 mg increased acetylcholine synthesis. The effects were greatest 15 minutes after injection. Gamma aminobutyric acid injected intraventricularly in doses of 0.6 mg increased the activity of choline acetyltransferase but had no effect on the activity of choline esterase.
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PMID:Gamma aminobutyric acid effect on acetylcholine level and metabolism in rat cerebral cortex. 737 94

Following sequential intraocular transplantations of areas containing NE cell bodies (locus coeruleus or superior cervical ganglion) and of NE fiber target areas (hippocampus), both pieces mature in a manner analogous to that observed for individual transplants. NE-containing nerve fibers, derived from either LC or SCG transplants, can be seen to invade the hippocampal formation. When LC is used, the invading fibers markedly hyperinnervate the hippocampus while SCG-derived fiber densities approximate those seen with innervation from the adrenergic ground plexus of the iris. Electrophysiological recordings from neurons in the LC reveal an atropine-sensitive excitatory response to illumination, suggesting innervation of the LC by cholinergic nerve fibers from the iris. This is supported by the fact that dense cholinesterase-positive staining can be found in the LC piece. Application of an epileptogenic agent, such as penicillin, results in a marked excitation of neurons in the LC without inducing epileptiform activity in the hippocampus. In contrast, single hippocampal grafts seize readily after penicillin. Local application of the inhibitory agent GABA into the LC allows penicillin-induced epileptiform activity to generate in the hippocampus, suggesting that functional inhibitory innervation develops between NE fibers derived from LC and pyramidal neurons in the hippocampus. Supporting this, subsequent excitation of LC neurons by iontophoresis of glutamate terminates the hippocampal seizure. Prior administration of reserpine (2.5 mg/kg) disrupts the inhibitory influence of LC innervation on the hippocampal EEG following penicillin. After reserpine, the hippocampal portions of double grafts behave like single hippocampal transplants. It is concluded that sequential transplantations of cell body and target regions of the CNS to the anterior chamber of the eye creates a functional, yet isolated, neuronal pathway which can be utilized to study the development of neuronal connections.
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PMID:Conditions for adrenergic hyperinnervation in hippocampus: II. Electrophysiological evidence from intraocular double grafts. 739 24

Gamma-aminobutyric acid (GABA) injected into the lateral ventricles of rat bran in a dose of 600 microgram raised the level and increased the synthesis of acetylcholine (ACh) raising also the activity of choline acetyltransferase (ChAc) but had no effect on the activity of cholinesterase (AChE) in rat striatum. Bucuculline (Bk) in doses of 10 mirogram i.c.v reduced ACh synthesis and in 50 and 10 microgram doses reduced the activity of ChAc. No Bk effect on AChE activity was demonstrated. The observed effects of GABA were abolished by pretreatment with Bk in doses of 1, 5 or 10 microgram.
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PMID:Gamma-aminobutyric acid and bicuculline effects on acetylcholine metabolism in the striatum in rats. 744 42

Rats trained on a Delayed Matching To Position (DMTP) task displayed mediating behavior during delays to solve the task. Infusion of the cholinergic antagonist scopolamine into the medial Prefrontal Cortex area (mPFC), dose dependently impaired performance independent of delay. These results indicate that scopolamine does not specifically affect working memory. Infusion of the cholinesterase inhibitor physostigmine, muscarinic subtype receptor antagonists, the dopamine (D1) antagonist SCH23390, and of the GABA-A receptor antagonist bicuculline, did not affect performance in the DMTP task. In a post-hoc analysis scopolamine was found to impair discriminability in a delay-dependent manner only in animals that used mediating behavior in the majority of the trials. Furthermore, a time sampling method indicated that scopolamine infusions into the mPFC disrupted mediating behavior during the task. Results suggest that cholinergic systems in the mPFC play a role in directing attention to task relevant behavior.
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PMID:Effects of infusion of cholinergic drugs into the prefrontal cortex area on delayed matching to position performance in the rat. 868 Aug 52

Sensitivity of brain muscarinic acetylcholine receptors to the agonists was examined in nicotine tolerant animals which were developed by acutely repeated injections of nicotine. In conscious rats, the dose-response curves of muscarinic agonists arecoline and pilocarpine, cholinesterase inhibitors soman and physostigmine rather than GABA receptor antagonist pentylenetetrazol or glycine receptor antagonist strychnine for producing EEG seizures were shifted leftwards by acutely repeated injections of nicotine. This phenomenon could be prevented by nicotinic antagonist mecamylamine. Similar results were obtained in acute nicotine tolerant mice and rabbits. In other experiments, the dose-response curve of arecoline-induced convulsions or oxotremorine-induced tremors was also shifted leftwards, and the durations of arecoline- and oxotremorine-induced tremors were prolonged in acute nicotine tolerant mice. In addition, the effects of arecoline for producing down-regulation of muscarinic receptors of rat cerebrum and hippocampus rather than brain stem were potentiated in acute nicotine tolerant rats. It is concluded that the sensitivity of brain muscarinic receptor to its agonists is increased in acute nicotine tolerant rats, mice and rabbits.
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PMID:Regulatory effects of acutely repeated nicotine treatment towards central muscarinic receptors. 889 Sep 20

Modes of action of anthelmintic drugs are described. Some anthelmintic drugs act rapidly and selectively on neuromuscular transmission of nematodes. Levamisole, pyrantel and morantel are agonists at nicotinic acetylcholine receptors of nematode muscle and cause spastic paralysis. Dichlorvos and haloxon are organophosphorus cholinesterase antagonists. Piperazine is a GABA (gamma-amino-butyric acid) agonist at receptors on nematode muscles and causes flaccid paralysis. The avermectins increase the opening of glutamate-gated chloride (GluCl) channels and produce paralysis of pharyngeal pumping. Praziquantel has a selective effect on the tegument of trematodes and increases permeability of calcium. Other anthelmintics have a biochemical mode of action. The benzimidazole drugs bind selectively to beta-tubulin of nematodes, cestodes and fluke, and inhibit microtubule formation. The salicylanilides: rafoxanide, oxyclozanide, brotianide and closantel and the substituted phenol, nitroxynil, are proton ionophores. Clorsulon is a selective antagonist of fluke phosphoglycerate kinase and mutase. Diethylcarbamazine blocks host, and possibly parasite, enzymes involved in arachidonic acid metabolism, and enhances the innate, nonspecific immune system.
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PMID:Modes of action of anthelmintic drugs. 926 48

Aging-, disease- and medication-related imbalance of central dopaminergic neurons causes functional impairment of cognition and neuropsychological delirium in humans. We attempted to develop a new delirium model using the direct dopamine agonist, apomorphine, and a choice reaction performance task performed by middle-aged rats. The psychological properties of the model were assessed by determining behavioral measures such as choice reaction time, % correct and % omission. Apomorphine (0.03-0.3 mg/kg s.c.) produced a dose-dependent impairment of task performance. The dose of 0.1 mg/kg prolonged choice reaction time, decreased % correct and increased % omission, indicating that rats had attentional deficits and a reduced arousal or vigilance but no motor deficits or reduced food motivation. This psychological and behavioral impairment of performance resembled that of clinically defined delirium. In this model, the cholinomimetic, aniracetam (10 mg/kg p.o.), reversed the performance impairment induced by apomorphine. Its two metabolites, 2-pyrrolidinone (10 and 30 mg/kg p.o.) and N-anisoyl-gamma-aminobutyric acid (GABA, 10 mg/kg p.o.), effectively reversed the performance impairment as the intact drug did. Another pyrrolidinone derivative, nefiracetam (10 and 30 mg/kg p.o.), tended to worsen the apomorphine effect. The cholinesterase inhibitor, tacrine (10 mg/kg p.o.), markedly worsened all of the behavioral measures. Neuroleptics, haloperidol (0.025 mg/kg s.c.), tiapride (30 mg/kg p.o.) and sulpiride (10 and 30 mg/kg p.o.), antagonized the apomorphine effect. The present results suggest that apomorphine-induced behavioral disturbances in the choice reaction performance task seems to be a useful delirium model and aniracetam may improve delirium through the action of 2-pyrrolidinone and N-anisoyl-GABA, presumably by facilitating dopamine release in the striatum by acting as an AMPA or metabotropic glutamate receptor agonist.
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PMID:Apomorphine-induced hypoattention in rats and reversal of the choice performance impairment by aniracetam. 954 78

Recent data indicate that the neurotoxic effects of organophosphate compounds, including those of the nerve agents VX and sarin, are not solely due to irreversible cholinesterase inhibition. In this study we applied the patch clamp technique to hippocampal neurons in culture and slices to investigate the effects of VX, sarin and huperzine A on transmitter release and the mechanisms related with such effects. The nerve agents VX and sarin at very low concentrations significantly reduced the evoked release of GABA and glutamate. This effect was dependent of the activation of muscarinic receptors. In the presence or absence of the Na(+)-channel blocker tetrodotoxin (TTX), VX increased the frequency of spontaneous glutamate and GABA-induced postsynaptic currents. The effect of VX on TTX-insensitive spontaneous currents appears to be unrelated to cholinesterase inhibition, because it could be detected even after cholinesterase was blocked by high concentrations of the nerve agent soman. The ability of the nerve gases to decrease evoked release of GABA and increase spontaneous transmitter release may underlie some of the neurotoxic effects of the compounds. Huperzine A did not affect spontaneous or evoked release of GABA and glutamate, suggesting that this compound may be a pure cholinesterase inhibitor and had no effect on postsynaptic GABAA or AMPA receptors.
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PMID:An analysis of low level doses of cholinesterase inhibitors in cultured neurons and hippocampal slices of rats. 1002 11

Extracellular recordings were obtained from the ganglion cell (GC) layer during correlated spontaneous bursting activity (SBA) in the immature turtle retina. Pharmacological agents were bath-applied, and their effects on burst and correlation parameters were determined. SBA requires synaptic transmission. It was blocked in the presence of curare and mecamylamine, two cholinergic nicotinic antagonists, and enhanced with neostigmine, a cholinesterase inhibitor. SBA was profoundly inhibited during blockade of glutamatergic receptors with the broad spectrum antagonist kynurenate and it vanished with 6,7-dinitroquinoxaline-2-3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), two AMPA/kainate receptor antagonists. Blockade of NMDA receptors with D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5) led only to a modest reduction in SBA. Blockade of GABAA receptors with bicuculline prolonged the duration of the bursts. Inhibition of GABA uptake with nipecotic acid led to a decrease in burst rate. Blockade of K+ channels with cesium (Cs+) and tetraethylammonium (TEA) led to a dramatic decrease in excitability. Burst propagation between neighboring GCs was reduced by K+ channel blockade. Gap junction blockade had no consistent effect on bursts or correlation parameters. None of these drugs had a strong effect on the refractory period between bursts. We conclude that correlated SBA in immature turtle GCs requires both cholinergic nicotinic and glutamatergic (mainly through AMPA/kainate receptors) synaptic transmission. GABAergic activity modulates the intensity and the duration of the bursts. Extracellular K+ is involved in lateral activity propagation and increases retinal excitability, which may be required for burst generation.
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PMID:Spontaneous activity in developing turtle retinal ganglion cells: pharmacological studies. 1023 19


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