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

---

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

A 28 year old man with a stable permanent idioventricular rhythm of 80 to 85 beats/min, with all the characteristics of a pacemaker, is described. This pacemaker was slowed by maneuvers that enhanced vagal tone, including carotid sinus massage, the postrelease phase of the Valsalva maneuver and phenylephrine. The pacemaker was also slowed by a cholinesterase inhibitor (edrophonium hydrochloride) and accelerated by a muscarinic receptor blocking drug (hyoscine butylbromide). The actions of these maneuvers and agents were independent of sympathetic tone as propranolol pretreatment did not alter their effects. Similarly, propranolol did not affect the pacemaker rate. The pacemaker was not dependent on a slow inward current because verapamil did not affect its rate. The pacemaker accelerated in response to increased sympathetic tone induced by exercise and upright tilting and to the adrenergic agonist isoproterenol. The pacemaker was localized to the high posterior septal region of the left ventricle underneath the mitral valve. This report describes in a man an idioventicular pacemaker that is innervated by sympathetic and vagal fibers and responsive to alterations in tone of both limbs of the autonomic nervous system. It offers the first clear proof that a ventricular pacemaker can be innervated and controlled by the vagus nerve and provides its location.
...
PMID:Modulation of an idioventricular rhythm by vagal tone. 272 81

Mouse N1E-115 neuroblastoma cells were used to study carbachol induced changes in muscarinic cholinergic parameters. Cells were treated with carbachol (1 mM) for up to 96 hours. The number of muscarinic receptors, measured in 3H-3-quinuclidinyl benzilate binding experiments, decreased approximately 50% after 4 hours exposure to carbachol. This was followed by an increase in binding sites, and after 24 hours the number of binding sites was the same as in control cells. The changes observed in the choline esterase activity followed the same pattern. The increase in number of binding sites was not dependent on protein synthesis, while the increase in choline esterase activity was. The muscarinic receptor-stimulated uptake of 45Ca2+ showed an initial decrease, which was followed by a significantly increased basal uptake of 45Ca2+. It is suggested that all these changes are adaptations of long time exposure to carbachol.
...
PMID:Exposure to carbachol induces several changes in muscarinic cholinergic parameters in N1E-115 mouse neuroblastoma cells. 335 74

Potential age-related differences in the response of Fischer 344 rats to subchronic treatment with diisopropylfluorophosphate (DFP) were evaluated in terms of brain cholinesterase (ChE) inhibition and muscarinic receptor sites. Male 3- and 24-month old rats were sc injected with sublethal doses of DFP (first dose 1.6, subsequent doses 1.1 mg/kg on alternate days) for 2 weeks and killed 48 hrs after the last treatment. In the cerebral cortex, hippocampus and striatum of control rats a significant age-related reduction of ChE and of maximum number of 3H-QNB binding sites (Bmax) was observed. The administration of DFP to senescent rats resulted in more pronounced and longer lasting syndrome of cholinergic stimulation, with marked body weight loss and 60% mortality. The percentage inhibition of brain ChE induced by DFP (over 80% in all regions) did not differ between young and senescent rats. As expected, in young rats DFP caused a significant decrease of Bmax (without apparent changes in affinity), which in the cerebral cortex reached about 40%. In the surviving senescent rats, the percentage decrease of Bmax due to DFP with respect to age-matched controls was very similar to that of young animals, especially in the cerebral cortex. Thus, there is great variability in the response of aged rats to DFP treatment, from total failure of adaptive mechanisms resulting in death to considerable muscarinic receptor plasticity. The data support the view that the ability of central neurotransmitter systems to compensate for pathological or xenobiotic induced insult is an essential part of the aging process.
...
PMID:Muscarinic receptor plasticity in the brain of senescent rats: down-regulation after repeated administration of diisopropyl fluorophosphate. 338 96

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.
...
PMID:Modification of the effects of muscarinic agonists by reversible and irreversible anticholinesterase compounds in the guinea pig atrium. 351 25

Muscarinic acetylcholine receptors in organotypic slice cultures of hippocampus of the rat, have been examined using the tritiated muscarinic antagonist quinuclidinylbenzilate [( 3H]QNB) as a as a marker. Maximum specific binding of [3H]QNB in mature explants of hippocampus amounted to 316 fmol/mg protein and a dissociation constant (KD) of 185 pM was determined. Scatchard analysis suggested binding to one single binding site. In younger cultures smaller KDs were registered. This decrease in ligand affinity in maturer cultures possibly reflects a decrease in the turnover of acetylcholine. Muscarinic antagonists inhibited the total binding of [3H]QNB significantly, whereas muscarinic agonist, nicotinic antagonists and cholinesterase inhibitors had no influence whatsoever on the total binding of [3H]QNB. The content of muscarinic acetylcholine receptors varied between cultures with explants from different brain areas: hippocampus greater than striatum greater than septum greater than spinal cord greater than cerebellum. These in vitro results are generally in good agreement with results obtained in situ by other investigators and suggest that the binding of [3H]QNB observed in these cultures is indeed correlated to specific muscarinic receptor sites.
...
PMID:Muscarinic receptors in slice cultures of rat brain. 370 72

The effects of various doses of physostigmine (Phy) on the activity of acetylcholinesterase (AChE) in plasma, cerebrospinal fluid (CSF) and brain were studied in beagle dogs. Two routes of administration were compared: intravenous (i.v.) and intracerebroventricular (i.c.v.). With intracerebroventricular administration, over 90% inhibition of the activity of AChE in CSF was reached within 5 min of injection at all doses (10-120 micrograms). Even at the smallest dose (10 micrograms), 50% inhibition of activity of the enzyme in CSF was still present at 90 min. The activity of AChE in plasma was only minimally inhibited by intraventricular administration of physostigmine. A different response was obtained following intravenous administration of physostigmine (250-1000 micrograms). The activity of AChE in plasma was inhibited but the activity of AChE in CSF was increased (36-80% at 180 min). This increase was dose-dependent and was blocked by pretreatment with atropine (1.5 mg i.v.) which suggests the involvement of a muscarinic receptor mechanism. The time course of the accumulation and regional distribution of [3H]physostigmine in brain also varied with the route of administration. At 5 min, with intravenous administration, physostigmine (1000 micrograms) reached greater concentrations and caused greater inhibition of AChE in the cortex. With intraventricular administration, physostigmine (80 micrograms) reached greater concentrations in two regions adjacent to the ventricular surface: the striatum and hippocampus. These regions also showed greater inhibition of the activity of AChE. Moderate to severe symptoms of cholinergic hyperactivity were seen only with the largest intraventricular dose (120 micrograms). This study suggests that intraventricular administration of physostigmine, a reversible inhibitor of cholinesterase (ChE), may offer distinct advantages over intravenous administration. Inhibition of acetylcholinesterase in CSF was more pronounced and persisted longer when physostigmine was administered directly into the CSF than when given intravenously. The implications of this study for a cholinergic therapy of Alzheimer's disease are discussed.
...
PMID:The effects of physostigmine on acetylcholinesterase activity of CSF plasma and brain. A comparison of intravenous and intraventricular administration in beagle dogs. 378 84

N1E-115 neuroblastoma cells were grown in the absence or presence of atropine (1 microM) for 9 days. After 9 days membranes were prepared from control and atropine-treated cells. They were stored frozen until some markers of muscarinic cholinergic function were measured. Atropine treatment increased the number of muscarinic receptors from 100 +/- 10 fmol/mg protein to 145 +/- 20 fmol/mg protein, decreased the cholinesterase activity from 3.5 +/- 2.0 U/mg protein to 1.0 +/- 0.5 U/mg protein and increased the choline acetyltransferase activity from 0.25 +/- 0.13 pmol [3H]acetylcholine synthesized/min X mg protein to 1.80 +/- 0.59 pmol [3H]acetylcholine synthesized/min X mg protein. It is suggested that all these changes are correlates of muscarinic receptor supersensitivity.
...
PMID:Long time treatment of N1E-115 neuroblastoma cells with atropine induces changes in markers of muscarinic cholinergic function. 396 Mar 99

Converging lines of evidence indicate an important role for the basal forebrain cholinergic system in memory processes. The principal origin of the cholinergic projection to the neocortex appears to be the magnocellular neurons in the region of the nucleus basalis of Meynert (NbM). We examined the effects of bilateral lesions of the NbM on retention of shock avoidance training by stereotaxically injecting rats with 0.5 microliter of ibotenic acid (14 micrograms/microliter) into the NbM. Two weeks later rats were given passive avoidance training and tested for retention of the original avoidance habit 5 min, 30 min, or 24 hr later. Rats with lesions of the NbM showed significantly impaired shock avoidance performance compared to non-operated controls at both 30 min and 24 hr, but not at 5 min after training. Lesioned animals also showed a significant decrease in cortical choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities. No differences in muscarinic receptor binding or plasma cholinesterase activity was observed. The results demonstrate the usefulness of NbM lesions as a model for studying the role of the basal forebrain cholinergic system in memory processes.
...
PMID:Further characterizations of the nature of the behavioral and neurochemical effects of lesions to the nucleus basalis of Meynert in the rat. 402 31

Cholinesterase inhibitors are known to potentiate the effects of acetylcholine (ACh) and vagal stimulation on the myocardium. The studies presented here demonstrate that cholinesterase inhibitors (ChEI) also have activity in isolated atria in the absence of extrinsic cholinergic stimulation and that, depending on the ChEI, either indirect stimulation or direct blockade of cardiac muscarinic receptors can occur. Muscarinic agonists inhibit cyclic AMP formation in atria and the ChEIs physostigmine, neostigmine and echothiophate likewise produce a marked attenuation of isoproterenol-stimulated cyclic AMP accumulation The effect of physostigmine appears to result from muscarinic receptor activation by endogenous ACh as it is blocked by atropine. In contrast, the ChEI ambenonium does not stimulate but instead blocks muscarinic receptors coupled to cyclic AMP accumulation. Radioligand binding studies provide direct evidence that both ambenonium and demecarium are relatively potent muscarinic receptor antagonists, whereas physostigmine and other ChEI have little direct receptor activity. Physostigmine and ambenonium also have different effects on heart rate in vivo, the former potentiating and the latter apparently blocking vagal tone. The inhibition of cyclic AMP formation produced by physostigmine can be used as a measure of the concentration of endogenous ACh available at muscarinic receptor sites. Physostigmine blocks cyclic AMP formation in atria incubated in the absence of calcium or in the presence of tetrodotoxin, suggesting that endogenous ACh is spontaneously released in the absence of neuronal activity or depolarization-secretion coupling.
...
PMID:Activation and blockade of cardiac muscarinic receptors by endogenous acetylcholine and cholinesterase inhibitors. 628 18

In unanaesthetized dogs iv administration of the cholinesterase inhibitor eserine (0.5 mg) or the cholinergic muscarinic receptor agonist oxotremorine (0.25 mg) induced a clear-cut rise in plasma canine growth hormone (cGH) levels. Complete suppression of the GH-releasing effect of eserine and oxotremorine was induced by blockade of cholinergic muscarinic receptors by atropine (80 or 20 micrograms/kg, 30 min before) but not by scopolamine-N-butyl bromide (0.8 mg/dog, 30 min before), an anticholinergic drug which does not cross the blood brain barrier (BBB). In contrast, activation of cholinergic nicotinic receptors by nicotine (6 mg) failed to alter resting cGH concentrations, and pre-treatment with the nicotinic receptor blocker mecamylamine (5 mg, 30 min before) did not counteract the GH-releasing effect of eserine. Other cholinomimetic drugs, e.g. pilocarpine, 4-aminopyridine, carbachol and bethanechol failed to induce a rise in plasma cGH concentrations. These data indicate that: 1) cholinergic muscarinic but not nicotinic receptors located in the central nervous system (CNS) inside the BBB play a facilitatory role in tonic cGH release; 2) pharmacologically distinct muscarinic receptors may exist in the CNS.
...
PMID:Effect of agonists and antagonists of cholinergic neurotransmission on growth hormone release in the dog. 630 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---