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

THA (9-amino, 1,2,3,4-tetrahydroacridine; tacrine) is currently under study as a cholinesterase (ChE) inhibitor in Alzheimer disease. In this study, a sensitive radiometric assay for THA inhibition of human plasma ChE, suitable for detection of effects of orally administered drug, is described. The assay is sensitive in a range of 4-50 ng/ml plasma. Reversibility of the inhibition permits distinguishing of drug effects on ChE from changes in amount of enzyme synthesized during treatment.
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PMID:Estimation of plasma tacrine concentrations using an in vitro cholinesterase inhibition assay. 278 91

gamma-Glutamyltransferase (EC 2.3.2.2; gamma-GT) may be important in the transport of amino acids or peptides across the blood-brain barrier. Gamma-GT activities were the same in cortical samples from Alzheimer and age-matched control brains, and there was no correlation between gamma-GT and choline acetyltransferase (ChAT) or acetylcholinesterase (AChE) levels, both of which were significantly reduced in the Alzheimer samples. ChAT and AChE activities were significantly correlated in both groups. ChAT showed a negative correlation with age in the controls and a positive correlation in the Alzheimer group. The opposite was true for gamma-GT, although the correlations were of low significance. The results do not lend any support to the hypothesis of a defect in the blood-brain barrier in Alzheimer disease.
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PMID:gamma-Glutamyltransferase: normal cortical levels in Alzheimer disease. 289 37

Cholinergic neurons are unique among cells since they alone utilize choline not only as a component of major membrane phospholipids, such as phosphatidylcholine (Ptd-Cho), but also as a precursor of their neurotransmitter acetylcholine (AcCho). It has been hypothesized that choline-phospholipids might serve as a storage pool of choline for AcCho synthesis. The selective vulnerability of cholinergic neurons in certain neurodegenerative diseases (e.g., Alzheimer disease, motor neuron disorders) might result from the abnormally accelerated liberation of choline (to be used as precursor of AcCho) from membrane phospholipids, resulting in altered membrane composition and function and compromised neuronal viability. However, the proposed metabolic link between membrane turnover and AcCho synthesis has been difficult to demonstrate because of the heterogeneity of the preparations used. Here we used a population of purely cholinergic cells (human neuroblastoma, LA-N-2), incubated in the presence of [methyl-3H]methionine to selectively label PtdCho synthesized by methylation of phosphatidylethanolamine, the only pathway of de novo choline synthesis. PtdCho, purified by thin-layer chromatography, contained 90% of the label incorporated into lipids, demonstrating that LA-N-2 cells contained phosphatidylethanolamine N-methyltransferase. Three peaks of radioactive material that cochromatographed with authentic Ac-Cho, choline, and phosphocholine were observed when the water-soluble metabolites of the [3H]PtdCho were purified by high-performance liquid chromatography. Their identities were ascertained by subjecting them to enzymatic modifications with acetylcholinesterase, choline oxidase, and alkaline phosphatase, respectively. The results demonstrate that AcCho can be synthesized from choline derived from the degradation of endogenous PtdCho formed de novo by methylation of phosphatidylethanolamine.
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PMID:Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line. 347 63

We measured acetylcholinesterase (AChE) and butyrylcholinesterase activities in the lumbar cerebrospinal fluid (CSF) of 39 patients with dementia of Alzheimer type and 21 age-matched controls. The mean lumbar CSF AChE activity in our patients did not differ significantly from that of controls. The 7S and 11S molecular forms were also unchanged. When CSF was analyzed at six-month intervals, there was no significant decline in AChE activity over a span of 12 months. Our results and those of previous studies demonstrate that CSF AChE is not a useful diagnostic marker of Alzheimer disease.
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PMID:Cholinesterases in cerebrospinal fluid. A longitudinal study in Alzheimer disease. 382 96

Eight patients with early Alzheimer disease were treated with gradually increasing multiple daily doses of oral physostigmine and supplemental lecithin. Six individuals showed improvement in total recall and retrieval from long-term storage (LTR), with a decrease in intrusions (a measure of inaccurate recall). The optimal individual dose was either 2.0 or 2.5 mg of physostigmine for each responding patient. Results of this open trial were subsequently replicated during a double-blind crossover trial comparing physostigmine treatment to placebo. All six patients again demonstrated improvement in total recall and LTR, with a decrease in intrusions. The decrease in intrusions was strongly correlated with increasing inhibition of cholinesterase activity in cerebrospinal fluid, suggesting that the degree of improvement in the patient's memory was related to the amount of physostigmine that reached the brain. Other neurotransmitters and metabolites in cerebrospinal fluid were unaffected by the physostigmine therapy, suggesting a specific effect of physostigmine on the cholinergic system. The results suggest that small oral doses of physostigmine combined with lecithin ingestion have therapeutic benefit for some patients with Alzheimer disease.
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PMID:Oral physostigmine and lecithin improve memory in Alzheimer disease. 634 34

Choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities were measured in spinal cord homogenates from rabbits with aluminum-induced neurofibrillary degeneration and a group of saline-treated, age-matched controls. All aluminum-treated animals showed neurofibrillary changes in the spinal cord, but CAT and AChE activities were not significantly different from levels in control animals. These results are at variance with the greatly reduced activity of these enzymes observed in Alzheimer disease and senile dementia of the Alzheimer type.
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PMID:Central cholinergic activity in aluminum-induced neurofibrillary degeneration. 739 28

In previous investigations, we have demonstrated that cholinesterase inhibitors such as physostigmine (PHY) and heptylphysostigmine (HEP) elicit a significant and simultaneous increase in acetylcholine (ACh) and norepinephrine (NE) levels in the rat cortex. This effect is enhanced by idazoxan, a selective alpha-2 antagonist. These data suggest that a combination of cholinergic and adrenergic drug may improve the pharmacological effect of the cholinesterase inhibitor on cortical neurotransmitters such as ACh-NE. In order to obtain additional information on cortical cortical neurotransmitter interaction, we tested, in the cerebral cortex of the rat, the effect of PHY and HEP in animals pretreated with clonidine (CLO), a selective alpha-2 agonist, on ACh, NE, dopamine and 5-hydroxytryptamine) extracellular levels. We detected no effect of systemic or intracortical CLO administration of ACh levels, but NE, dopamine and 5-hydroxytryptamine levels were all decreased. Systemic coadministration of CLO and PHY significantly elevated ACh levels and decreased NE, dopamine and 5-hydroxytryptamine levels. Systemic coadministration of CLO and HEP produced a significant elevation in ACh levels. Comparison between the two treatment combinations shows that, although CLO coadministration reduces the effect of PHY on ACh levels, HEP administered to animals pretreated with CLO produces a stronger effect than HEP alone. A possible explanation for this difference is the variation in duration of the two drugs on ACh elevation and muscarinic receptor desensitization. As a result of the alpha-2 agonist cholinesterase inhibitor coadministration, our data suggest that such a combination does not represent an advantage as a therapeutical alternative for treatment of cognitive impairment in Alzheimer disease patients.
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PMID:Effects of cholinesterase inhibitors and clonidine coadministration on rat cortex neurotransmitters in vivo. 756 54

We examined whether cholinesterase inhibitors (ChEI) could alter the release of amyloid precursor protein (APP) from superfused brain cortical slices of the rat. Three ChEI, both reversible and irreversible, were tested for their ability to enhance the release of nonamyloidogenic soluble derivatives (APPs). These included: physostigmine (PHY), heptyl-physostigmine (HEP) and 2,2-dichloro-vinyldimethyl phosphate (DDVP), at concentrations producing cholinesterase (ChE) inhibition ranging from 5% to 95%. All three ChEI elevated APPs release significantly above control levels. Electrical field stimulation significantly increased the release of APPs within 50 min. Similar increase was observed after muscarinic receptor stimulation with bethanechol (BETHA). Tetrodotoxin (TTX) completely blocked the effect of electrical stimulation. These findings suggest that administration of ChEI to Alzheimer's disease (AD) patients may have a neuroprotective effect by activating normal APP processing.
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PMID:Cholinesterase inhibitors increase secretion of APPs in rat brain cortex. 760 15

Many theories have been advanced but the true physiological function for serum cholinesterase has still not been identified. Evidence has been presented for the abnormal expression of cholinesterase genes in many types of human tumors. Cholinesterase measurements are still used to monitor exposure to organophosphate insecticides and their clinical application requires a good understanding of the inter and intra-individual variation, as well as some knowledge of the time sequence between exposure and measurement of the cholinesterase activity. The use of serum cholinesterase measurement in liver disease varies in different countries. A case has not been made for the cost-effectiveness of adding serum cholinesterase as part of a screening procedure for the diagnosis of liver disease. During the last 10 years much information has been obtained on the molecular biology and genetics of acetylcholinesterase and butyrylcholinesterase, distinct enzymes encoded by two different, but related genes. It has been established that BChE is included by a single gene which corresponds to the E1 locus. The complete amino acid sequence of human serum cholinesterase and the location of disulfide bonds within the sequence have been described. The molecular basis of many variants of human serum cholinesterase has been described in detail. It is not rare for multiple mutations to occur within a single butyrylcholinesterase gene or there may be combination of mutations. At least 11 silent variants of human butyrylcholinesterase have been identified. There still exists a wide variety of substrates and analytical conditions for butyrylcholinesterase measurement in a number of clinical situations. No real evidence has been provided for clinical value for their use in the diagnosis of Alzheimer disease or monitoring the use of cholinesterase inhibitors in the treatment of pre-senile dementia of Alzheimer type. However, the insights from molecular biology technology may well open up more challenges in a variety of clinical situations.
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PMID:Clinical and analytical considerations in the utilization of cholinesterase measurements. 766 82

Transection of the fimbria-fornix bundle in adult rats results in degeneration of the septohippocampal cholinergic pathway, reminiscent of that occurring in aging as well as Alzheimer disease. We report here a study of the effect of a treatment with acetyl-L-carnitine (ALCAR) in three-month-old Fischer 344 rats bearing a partial unilateral fimbria-fornix transection. ALCAR is known to ameliorate some morphological and functional disturbances in the aged central nervous system (CNS). We used choline acetyltransferase (ChAT) and acetyl cholinesterase (AChE) as markers of central cholinergic function, and nerve growth factor (NGF) levels as indicative of the trophic regulation of the medio-septal cholinergic system. ChAT and AChE activities were significantly reduced in the hippocampus (HIPP) ipsilateral to the lesion as compared to the contralateral one, while no changes were observed in the septum (SPT), nucleus basalis magnocellularis (NBM) or frontal cortex (FCX). ALCAR treatment restored ChAT activity in the ipsilateral HIPP, while AChE levels were not different from those of untreated animals, and did not affect NGF content in either SPT or HIPP.
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PMID:Acetyl-L-carnitine restores choline acetyltransferase activity in the hippocampus of rats with partial unilateral fimbria-fornix transection. 779 6


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