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:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems where it often coexists with catecholamines and acetylcholine. Recently we have reported that human GAL (hGAL) in man depresses the release of norepinephrine (NE) and the responses to both assumption of upright posture and insulin-induced hypoglycemia. To gain an insight into the action of hGAL on sympathetic nervous system activity in man, we investigated the effects of a 60-min infusion (80 pmol/kg/min) of hGAL or saline on the release of NE, epinephrine (E) and pancreatic polypeptide (PP) induced by an acetylcholinesterase inhibitor, pyridostigmine bromide (PD), in nine healthy volunteers. PD (120 mg orally) induced a significant rise in plasma concentrations of NE (1.6 +/- 0.04 vs. 1.08 +/- 0.06 nmol/l), E (0.34 +/ 0.05 vs. 0.12 +/- 0.04 nmol/l) and PP (178.06 +/- 33 vs. 37.57 +/- 7.35 pmol/l), whilst it significantly reduced heart rate (HR; 61 +/- 2 vs. 71 +/- 4 beats/min). Changes in plasma levels of PP were determined as an indirect measure of amplification of endogenous cholinergic activity produced by PD. Administration of hGAL blunted the release of NE and PP evoked by PD. The mean (+/- SEM) area under the curve produced by PD of NE (50.05 +/- 3.97 nmol/l.90 min) and PP (8,692.87 +/- 1,724 pmol/l.90 min) was significantly (p < 0.001) reduced by hGAL infusion (2.65 +/- 1.57 nmol/l.90 min and 248.1 +/- 148 pmol/l.90 min, for NE and PP, respectively). hGAL failed to affect significantly the E release evoked by PD. hGAL was able to enhance HR significantly (104 +/- 5 vs. 69 +/- 3 beats/min), and completely prevented the PD-induced slowing of HR. Both PD and hGAL did not alter supine systolic and diastolic blood pressure. We conclude that hGAL significantly reduces the release of NE and PP stimulated by PD-induced enhancement of cholinergic activity. These findings are consistent with a functional interrelationship between GAL and the cholinergic system in man, and may suggest the participation of a cholinergic pathway in the galaninergic modulation of the autonomic nervous system.
...
PMID:Acute administration of human galanin in normal subjects reduces the potentiating effect of pyridostigmine-induced cholinergic enhancement on release of norepinephrine and pancreatic polypeptide. 893 Sep 40

The operating environment of the service personnel during the Persian Gulf War involved psychological, biological, and chemical elements including exposure to pesticides such as the insect repellent DEET (N,N-diethyl-m-toluamide) and the insecticide chlorpyrifos (O,O-diethyl O-3,5,6-trichloropyridinyl phosphorothioate) and to pyridostigmine bromide (PB,3-dimethylaminocarbonyloxy-N-methylpyridinium bromide) that was administered as a prophylactic agent against possible nerve gas attack. The present study was designed to determine the toxicity produced by individual or coexposure of hens 5 days/week for 2 months to 5 mg PB/kg/day in water, by gavage; 500 mg DEET/kg/day, neat, sc; and 10 mg chlorpyrifos kg/day in corn oil, sc. Coexposure to various binary treatments produced greater neurotoxicity than that caused by individual exposures and was characterized by severe neurologic deficit and neuropathological alterations. Also, neurotoxicity was further enhanced following concurrent administration of the three chemicals. Severe inhibition of plasma butyrylcholinesterase (BuChE) activity was produced in hens treated with PB (activity 17% of control) compared to those treated with chlorpyrifos (activity 51% of control) or DEET (activity 83% of control). BuChE inhibition was further increased in binary and tertiary treatment groups compared to individual treatment groups. In contrast, a significant inhibition of brain acetylcholinesterase (AChE) was produced in hens administered chlorpyrifos alone (activity 67% of control), while those given chlorpyrifos in combination with other compounds exhibited a significant inhibition of brain AChE activity ranging from 43 to 76%. Brain neurotoxicity target esterase (NTE) was not inhibited in any of the individual treatment groups or PB/DEET, but was significantly inhibited and had activity expressed as a percentage of control in groups administered combined chlorpyrifos with PB of 73% or DEET of 74% and in the tertiary treatment group of 71%. We hypothesize that test compounds may compete for xenobiotic metabolizing enzymes in the liver and blood and may also compromise the integrity of the blood-brain barrier, leading to an increase in their "effective concentrations" in the nervous system to levels equivalent to the toxic doses of individual compounds. This is consistent with the present observation of increases in (1) the inhibition of brain AChE and NTE, (2) the extent of neurologic dysfunction, and (3) the severity and frequency of neuropathologic lesions in the combined treatment groups compared to those administered individual compounds.
...
PMID:Increased neurotoxicity following concurrent exposure to pyridostigmine bromide, DEET, and chlorpyrifos. 895 50

Effect of diisopropylphosphorofluoridate (DFP), an irreversible cholinesterase (ChE) inhibitor, on compound action potential (CAP) of sciatic nerve in vitro was examined. Further, the role of cholinesterase reactivator (1 acetyl-4-hydroxy imino methyl pyridinium bromide; SPK-3) in reversing DFP-induced changes was also evaluated. Diisopropylphosphorofluoridate produced a dose-dependent depression of the CAP. A concentration as low as 0.01 microM DFP produced a 5% depression (P < 0.05) and the maximal depression (30% of control) was observed with 1 microM. The SPK-3 (up to 10 microM) had no effect on the CAP; SPK-3 (10 microM) antagonized the DFP-induced depression of the CAP partially but not after 1 microM DFP. However, the inhibitory concentration of DFP to produce 50% of the maximal depression (IC50) was 0.38 +/- 0.025 microM in the presence of SPK-3 (10 microM; n = 4), against 0.15 +/- 0.05 microM for DFP alone (n = 7). These IC50 values were significantly different (P < 0.05, Student's t-test). The DFP decreased nerve ChE activity by 41% in the absence of SPK-3 and by 31% in the presence of SPK-3. Although SPK-3 could not completely reactivate the inhibited enzyme, it seems reasonable to conclude that the DFP-induced depression of the action potential of sciatic nerve was mediated by inhibiting the ChE activity.
...
PMID:Diisopropylphosphorofluoridate-induced depression of compound action potential of frog sciatic nerve in vitro is mediated through the inhibition of cholinesterase activity. 895 95

Dysfunction of the autonomic nervous system is of prognostic value for sudden death after acute myocardial infarction. Although the use of beta-blockers to counteract the adrenergic hyperactivity has been shown to decrease mortality in these patients, there have been no reports on the role of cholinomimetic drugs in the prognosis of patients after myocardial infarction. The present study was designed to investigate the effect of the administration of pyridostigmine bromide, a reversible anti-cholinesterase agent, on cardiac cholinergic activity assessed by the resting and reflex heart rate responses. Eight healthy volunteers were submitted to a conventional 12-lead electrocardiogram to obtain resting heart rate, and to three non-invasive cardiovascular tests: respiratory sinus arrhythmia, Valsalva maneuver and 4-sec exercise test. On two different days and following a randomized cross-over double-blind protocol, the experiments were performed before and 120 min after oral administration of either pyridostigmine bromide (30 mg) or placebo. Pyridostigmine increase (P < 0.05) the duration of the R-R intervals at rest (pre: 898 +/- 30 msec; post: 1019 +/- 45 msec; pre-placebo: 916 +/- 26 msec; post: 956 +/- 28 msec; P > 0.05). Although the duration of the R-R intervals during the autonomic tests was also increased (P < 0.05), the derived indexes of maximal fluctuation during the maneuvers did not change. These results indicate that oral pyridostigmine produces tonic cardiac cholinergic stimulation while exerting no effect on its reflex changes. Further studies are needed to address the potential role of the administration of pyridostigmine in the prognosis of patients with acute myocardial infarction.
...
PMID:Resting and reflex heart rate responses during cholinergic stimulation with pyridostigmine in humans. 919 46

ApolipoproteinE (ApoE) genotype has recently been identified as a major risk factor for Alzheimer's disease (AD) but the mechanism(s) by which ApoE isoforms influence this disease remain unclear. Recent studies suggest that mice deficient in ApoE may exhibit impaired central cholinergic function. Since this neurotransmitter system has traditionally been associated with the pathogenesis of AD, we have further investigated the impact of ApoE gene deletion on this system. Female ApoE knockout (ko) mice, age 12 months, were compared with wild type littermate controls using a range of behavioural, biochemical and histochemical techniques. Pre-treatment with the cholinomimetic, donepezil (E2020; 2.5-5 mg kg-1 IP), produced significant hypothermia and induction of tremor in both wild type and ApoE ko mice. The magnitude of change did not significantly differ between the groups. Cognitive testing in the Morris water maze revealed that both wild type and ApoE ko mice could learn the location of a hidden escape platform with similar rates of acquisition and accuracy. Similarly, the behaviour of both genotypes proved indistinguishable in a Y-maze spontaneous alteration procedure. The protocols used for both cognitive tests were then shown to be sensitive to the disruptive effects of scopolamine (but not scopolamine methyl bromide). Following behavioural testing, choline acetyltransferase (ChAT) activity was measured in the hippocampus, frontal and entorhinal cortex and striatum. In each case there was no difference between the genotypes. In addition, coronal sections of striatum and anterior hippocampal regions of ApoE ko and wild type mice showed similar patterns of acetylcholinesterase (AChE) staining, with no qualitative or obvious quantitative difference. Finally, analysis of plasma cholesterol levels confirmed ApoE genotype. In conclusion, using a combination of behavioural, histochemical and biochemical measurements, we have failed to detect any significant differences in central cholinergic activity between wild type and ApoE ko mice.
...
PMID:Absence of central cholinergic deficits in ApoE knockout mice. 926 10

The involvement of muscarinic autoreceptors in the regulation of hippocampal acetylcholine levels during acetylcholinesterase inhibition was examined by perfusing the acetylcholinesterase inhibitor neostigmine bromide (10, 100 or 1000 nM) alone and in the presence of the muscarinic receptor antagonist atropine methylnitrate (10 microM), in resting and behaviourally-activated animals. In resting animals, local perfusion of neostigmine caused a dose-dependent increase in acetylcholine levels. Coadministration of atropine did not affect basal levels in the presence of 10 nM neostigmine, but increased acetylcholine levels approximately four and 11-fold in the presence of 100 nM and 1000 nM neostigmine, respectively. In animals which were behaviourally activated by handling, acetylcholine levels increased two- to three-fold in the presence of all neostigmine concentrations. However, the handling-induced increase in acetylcholine levels was somewhat smaller with 1000 nM neostigmine as compared to 10 nM neostigmine. Atropine had no effect on handling-induced acetylcholine output in the presence of 10 nM neostigmine, but caused greater and longer increases in the presence of 100 nM and 1000 nM neostigmine. These data indicate that acetylcholine levels are greatly reduced by autoinhibition at higher levels of acetylcholine esterase inhibition. The handling-evoked increase in acetylcholine levels is only moderately affected by the level of acetylcholinesterase inhibition, despite the participation of autoreceptors in the handling effect at higher levels of acetylcholinesterase inhibition.
...
PMID:Effects of neostigmine and atropine on basal and handling-induced acetylcholine output from ventral hippocampus. 948 38

This study was conducted to determine the pharmacokinetics and pharmacodynamics of pyridostigmine given as 30 mg of pyridostigmine bromide every 8 hours in healthy subjects. Plasma pyridostigmine concentration and red blood cell acetylcholinesterase activity were measured in blood samples collected during a 3-week period. Population analysis was performed using standard pharmacokinetic and pharmacodynamic models with the nonlinear mixed-effect modeling software (NONMEM). The pharmacokinetic model that best fit the pyridostigmine plasma levels was a two-compartment open model with first-order absorption, a lag time, and first-order elimination from the central compartment. The pharmacodynamic model that best fit red blood cell acetylcholinesterase activity was an inhibitory Emax model with an effect compartment linked to the central compartment. The results showed that the pharmacokinetics of pyridostigmine bromide are both gender and weight dependent. The pharmacodynamic effect does not lag significantly from the plasma concentration and returns to near normal within 8 hours. With the present dosage regimen of 30 mg every 8 hours, 30% of individuals may not have red blood cell acetylcholinesterase inhibition > 10% at the time of the trough.
...
PMID:Population pharmacokinetics and pharmacodynamics of pyridostigmine bromide for prophylaxis against nerve agents in humans. 954 61

Gulf War Syndrome has become a growing concern of US government, military Gulf war veterans and their families. It is suggested that research on genotype/phenotype of acetylcholinesterase and butyrylcholinesterase may help to discover the role of pyridostigmine bromide in the cause of Gulf War Syndrome.
...
PMID:Pyridostigmine bromide and Gulf War syndrome. 979 1

Adult male mice were treated with the reversible acetylcholinesterase inhibitor pyridostigmine bromide and its effect on the expression of beta-endorphin and alpha-melanotropin immunoreactivity in motoneurones was examined in the cervical and lumbar spinal cord. Administration of a single dose of either 0.4 micromoles/kg or 2.0 micromoles/kg body weight caused a significant increase in the incidence of beta-endorphin and alpha-melanotropin-immunoreactive motoneurones at 3h after the injection, in both the cervical and lumbar regions of the spinal cord. The immunoreactivity remained elevated for at least 5 days. There was a significantly higher increase in both beta-endorphin and alpha-melanotropin immunoreactive neurones at 3h after the higher dose compared to the lower dose, in both regions of the spinal cord. Repeated administration of a dose of 0.4 micromoles/kg once a day for three weeks caused increases in immunoreactive motoneurones in both regions. In the cervical region the increases were maintained for at least two weeks after the treatment was discontinued but in the lumbar region the levels had returned to normal by one week. A further dose of the drug administered at two weeks after the treatment period caused a significantly greater increase in the lumbar spinal cord than the same dose in untreated mice, indicating that a sensitization of the motoneurones had occurred. The effect of this drug on peptide expression in motoneurones may be secondary to its action to inhibit acetylcholinesterase at the neuromuscular junction.
...
PMID:The effect of pyridostigmine administration on the expression of pro-opiomelanocortin-derived peptides in motoneurones. 986 69

It has been suggested that toxicity to cocaine is related to the relative rate of cocaine metabolism by cholinesterases and to activation of cholinergic receptors either directly or by reflex mechanisms. We examined these possibilities by altering cholinesterase activity and blocking cholinergic receptors in rats prone or resistant to cocaine-induced cardiovascular toxicity. Rats were instrumented with a pulsed Doppler flow probe on the ascending aorta for measurement of cardiac output and cannulated for arterial pressure and heart rate determination. In conscious rats, cocaine (5 mg/kg iv) elicited pressor responses and a delayed bradycardia but cardiac output and systemic vascular resistance responses varied greatly between rats. Pretreatment with the nonspecific cholinesterase inhibitors physostigmine (0.1-0.2 mg/kg) or neostigmine (0.1 mg/kg) reduced the pressor response by diminishing the increase in systemic vascular resistance. In contrast, inhibition of cocaine metabolism with the selective plasma cholinesterase inhibitor tetraisopropyl pyrophosphoramide (0.5 mg/kg) or increasing cholinesterase activity with human butyryl cholinesterase (9.9 mg/kg iv) did not alter hemodynamic responses to cocaine. Administration of atropine methyl bromide (0.5-1 mg/kg iv) alone or with physostigmine to prevent the cholinomimetic effects of physostigmine reduced the cocaine-induced decrease in cardiac output noted in some animals. These data suggest that the cocaine-induced decrease in cardiac output observed in some rats is, at least in part, dependent on activation of muscarinic receptors. In addition, the rate of cocaine metabolism is not critical for the initial hemodynamic responses to cocaine in conscious rats.
...
PMID:Role of cholinergic receptors and cholinesterase activity in hemodynamic responses to cocaine in conscious rats. 988 83


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

---