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)

Dissociated cells from 13- and 17-day-old embryonic rat mesencephali have grown in primary cultures in order to compare the early and late influences of different agents--insulin, dexamethasone and nerve growth factor (NGF)--on the expression of cholinergic maturation process. We have studied cholin acetyltransferase (ChAT) activity, which is regarded as a specific marker for cholinergic function of the brain, and a widely used differentiation marker, the acetyl-cholinesterase (AchE) enzyme. Biochemical maturation of increasing specific activity of ChAT in both younger and older cells was taken into consideration. During cultivation the AchE activity was slightly increased in younger cells, but a dramatic decrease could be noted in older ones. Insulin in concentration from 10 to 27 micrograms mL-1 causes a significant inhibition in ChAT activity in comparison with the enzyme activity measured in control cultures (insulin ranging from 1 to 100 ng), independently of embryos age. This polypeptide hormone is able to enhance AchE activity in the cultured cells, especially in older ones. With continuous treatment of the culture with dexamethasone, a synthetic glucocorticoid, the ChAT activity in younger cells reaches a maximum curve by day 9 (nine). At this time the AchE activity shows a slighter, no significant increase than at any other time during cultivation. In cell cultures taken from 17-day-old embryos however dexamethasone treatment evoked a significant decrease in ChAT activity with a concomitant increase of AchE activity which was compared to insulin treatment. In spite of the fact that the NGF is able to enhance the ChAT activity, no significant alteration in AchE activity can be measured in younger cell cultures. These results suggest an uneven expression of the enzymes in embryonic rat mesencephali in the presence of above agents depending on the age of cells.
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PMID:Early and late hormonal modulation of cholinergic maturation in culture of embryonic mesencephali. 141 68

Neurons dissociated from septal area of fetal (E18-19) rat brain were grown 14-days in culture. Cholinergic neurons were identified by cytochemical demonstration of acetyl cholinesterase. It was shown that the nerve growth factor added to the culture medium (50 u/ml) has increased the size of cell body of AchE-positive neurons, mean total length and arborization of dendrites and also the dendritic tree area.
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PMID:[Effects of nerve growth factor on the development of the dendritic system of cholinergic neurons in dissociated culture of the rat septum]. 142 Dec 39

Neurons dissociated from septal area of fetal (E 18-19) rat brain were grown for 7 days in culture. Cholinergic neurons were identified by cytochemical demonstration of acetyl cholinesterase. Addition of the nerve growth factor to the culture medium (200 u/ml) increases the number of AChE-positive neurons, the size of the cell body and activity of AChE in these neurons.
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PMID:[The effect of nerve growth factor on cholinergic neurons in dissociated cultures of the septum pellucidum]. 205 13

Neurons dissociated from the septal area of fetal rat brains were grown in culture. Cholinergic neurons were identified by immunocytochemical visualization of choline acetyltransferase and cytochemical demonstration of acetyl cholinesterase. Choline acetyltransferase immunocytochemistry stained cell bodies and proximal processes while acetylcholinesterase cytochemistry visualized the entire neuron. Choline acetyltransferase-positive neurons could only be identified in cultures grown under conditions that produced the maximal choline acetyltransferase activity, measured biochemically. All of the choline acetyltransferase-positive neurons were double stained for acetylcholinesterase while only 6% of the acetylcholinesterase-positive cells were choline acetyltransferase negative in these cultures. These results indicate that acetylcholinesterase is a reliable marker for cholinergic cells in cultures of dissociated septal neurons. Being the more sensitive method, acetylcholinesterase staining was therefore used to identify cholinergic cells in cultures with choline acetyltransferase levels insufficient for immunocytochemical visualization of this enzyme. Addition of nerve growth factor or antibodies to nerve growth factor to the medium did not affect the number of cholinergic neurons surviving in culture. Furthermore, nerve growth factor and anti-nerve growth factor failed to influence the general morphological appearance and the number of processes of these neurons. However, nerve growth factor elevated the biochemically measured activity of choline acetyltransferase up to two-fold. The nerve growth factor-mediated increase in choline acetyltransferase activity was dose dependent with an ED50 of 10 ng/ml (4 X 10(-10) M). The increase was highly specific for nerve growth factor. It was blocked by anti-nerve growth factor, and epidermal growth factor, insulin and other control proteins failed to exert a similar effect. Nerve growth factor had to be present for at least 3 days in the culture medium to increase choline acetyltransferase activity, suggesting that the increase was due to an elevated choline acetyltransferase synthesis rather than to an activation of the enzyme.
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PMID:Nerve growth factor increases choline acetyltransferase but not survival or fiber outgrowth of cultured fetal septal cholinergic neurons. 397 85

PC12, a clonal line of rat pheochromocytoma, synthesizes, stores, and secretes dopamine and acetylcholine. The cells take up choline by a saturable process and rapidly convert the accumulated choline to acetylcholine. This choline transport has a Km of 12 microM, is Na+ and energy independent, and is relatively insensitive to hemicholinium-3 (IC50 approximately 50 microM). Different ionic conditions can modulate the choline transport. Uptake was increased by pretreatment with 55 mM K+ whereas it was decreased in the presence of 55 mM K+. Choline uptake had similar characteristics in PC12 cells that had been induced to extend neurites by treatment with nerve growth factor. In undifferentiated PC12 cells, storage of newly synthesized acetylcholine was found in bound and free compartments as evidenced from subcellular fractionation. The free pool had a faster turnover rate. Most of the newly synthesized acetylcholine was rapidly degraded in the absence of a cholinesterase inhibitor while continuous incubation with labeled choline resulted in a slow incorporation of newly labeled acetylcholine into a bound pool. The accumulation of acetylcholine in the bound pool, but not acetylcholine synthesis, was inhibited by each of several agents that are known to interfere with the generation or maintenance of proton electrochemical gradients. The newly synthesized acetylcholine could be released from PC12 cells by incubation of the cells with 55 mM K+. These properties indicate that PC12 cells are a good system for studying acetylcholine metabolism by secretory cells.
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PMID:Choline and acetylcholine metabolism in PC12 secretory cells. 728 37

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

Brain imaging techniques will in the future play an important role in the assessment of patients with neurogenerative disorders such as Alzheimer's disease (AD). An early diagnosis of AD is today hampered by lack of reliable diagnostic markers. Positron emission tomography (PET) permits the quantification and three-dimensional imaging of physiological variables. This provides the clinician with a non-invasive imaging technique which allows in vivo quantification of physiological processes in AD underlying dysfunction of cognition. PET studies regarding changes in cerebral blood flow and metabolism are rather consistent at least in moderate/advanced cases of AD. How early in the progress of the disease deficits in these parameters can be observed is still an open question. Longitudinal studies will here be important and especially in individuals with a family history of AD. Since deficits in cholinergic neurotransmission have been measured in autopsy AD brains attempts have also been made to visualized cholinergic activity in vivo. Nicotinic and muscarinic receptors have been visualized in normal and AD brains. A reduced uptake and binding of [11C]nicotine in the temporal and frontal cortices have been measured in AD patients by PET. Few treatment studies in AD have been evaluated by PET. Long-term treatment with the cholinesterase inhibitor tacrine increase the uptake of [11C]nicotine. Significant reduction in uptake between the two enantiomers (S)(-) and (R)(+)-[11C]nicotine has been observed compatible with a restoration of nicotinic receptors. Tacrine also significantly increased the glucose metabolism. PET studies indicate that long-term tacrine treatment in AD patients with mild dementia improves functional activities in brain. When an AD patient with moderate dementia was treated with nerve growth factor (NGF) PET studies revealed increase in cortical blood flow and nicotinic receptors. PET studies will in the future play an important role in the evaluation of new therapeutic drug strategies in AD.
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PMID:Clinical studies in Alzheimer patients with positron emission tomography. 790 47

The complex picture of age-associated brain cholinergic deficiency in humans and animals, and the possibilities of correcting it, are presented in this article. The changes that occur during ageing and senile dementias in cholinergic neurones and receptors and in the release and synthesis of acetylcholine are described and discussed. The drugs that have so far been administered to humans to correct cholinergic deficiency are listed and the effects of cholinesterase inhibitors, nerve growth factor and phosphatidylserine are discussed in some detail.
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PMID:The brain cholinergic system in ageing mammals. 831 16

Following the introduction of tacrine hydrochloride (Cognex) in the United States and several other countries, researchers are pursuing two broad therapeutic strategies for Alzheimer's disease (AD). The first involves identifying agents or combinations of agents whose actions can compensate for the considerable cerebral damage that has typically occurred by the time the diagnosis of AD is made. Such therapeutic approaches include the development of additional cholinesterase inhibitors, agents that work on the receptors of other systems damaged by the disease process, and anti-inflammatory and immunomodulatory agents. The second and ultimately more promising strategy involves the development of approaches to retard, halt, or even prevent disease progression. Such protective approaches, which depend on the development of more effective methods for predicting and diagnosing AD, include the administration of nerve growth factor and other neurotrophins and the use of pharmacologic or genetic interventions to limit amyloid deposition and the formation of neurofibrillary tangles.
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PMID:Treatment of Alzheimer's disease: future directions. 874 Oct

We have reported that the continuous infusion of anti-nerve growth factor (NGF) monoclonal antibody into the septum of rats produces neuronal dysfunction in the cholinergic system. Propentofylline has potent stimulatory effects on NGF synthesis/secretion in mouse astrocytes in vitro. To investigate the pharmacological effects of propentofylline, we used an animal model of dementia in which anti-NGF antibody was infused into the septum for 16 days via a mini-osmotic pump. The rats were treated with propentofylline orally once a day throughout the period during which performance in learning and memory tasks was observed. In the vehicle-treated dementia rats, learning and memory ability and choline acetyltransferase and cholinesterase activity were reduced compared to values in the control rats. The administration of propentofylline prevented the decreased learning capacity and the deficit in cholinergic marker enzyme activities. These results suggest that the use of NGF stimulators may provide a new approach to the treatment of dementia.
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PMID:Propentofylline prevents neuronal dysfunction induced by infusion of anti-nerve growth factor antibody into the rat septum. 883 Oct 96


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