Disease relevance of Ache

• By eliminating plasma CarbE (alpha-NA) as potential binding sites for paraoxon with either CBDP or iso-OMPA, paraoxon can exert its toxicity to a greater extent at its specific target site, the functionally important AChE at cholinergic synapses [1].
• In this study we used pheochromocytoma (PC12) cells, a noncholinergic cell line, rich in acetylcholinesterase (AChE) activity, to examine the effects of cholinesterase-inhibiting pesticides on neural differentiation [2].
• The results confirmed prior reports that hyperglycemia significantly enhances TBARS levels in brain and retinal tissue and decreases AChE and BChE activity [3].
• In this species, in contrast to the cat, the somata of essentially all ganglion cells of the superior cervical ganglion contain various but at least moderate concentrations of acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) and propionylcholinesterase (acylcholine acylhydrolase, EC 3.1.1.8) [4].
• Acetylcholinesterase induces neuronal cell loss, astrocyte hypertrophy and behavioral deficits in mammalian hippocampus [5].

Psychiatry related information on Ache

• Synthesis, in vitro pharmacology, and molecular modeling of very potent tacrine-huperzine A hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer's disease [6].
• The doses that improved AF64A-induced memory deficit were correlated to about 25-30% (huperzine A) and less than 10% (E2020, tacrine) inhibition of acetylcholinesterase (AChE) activity in the cortex and hippocampus [7].
• The reduction of acetylcholinesterase (AChE) activity in the brain has been measured in dementia disorders such as Alzheimer's disease and dementia with Lewy bodies using (11)C-labeled acetylcholine analogues, N-[(11)C]methylpiperidin-4-yl acetate and propionate, and positron emission tomography (PET) [8].
• The effects of electroconvulsive shock on the levels of acetylcholinesterase in several brain regions of the rat were studied [9].
• AChE activity and spontaneous locomotor activity returned to control values at 48 h [10].

High impact information on Ache

• DMSO (2%) inhibits the fusion of myoblasts to form multinucleate myotubes, the normal increases in activity of creatine phosphokinase (CPK) and acetylcholinesterase, and the synthesis of alpha-actin and acetylcholine receptor protein [11].
• Under these conditions acetylcholinesterase-staining (presumed cholinergic) fibres grow out from the septum into the hippocampus [12].
• ACh is rapidly degraded in the blood by acetylcholinesterase, so that ACh must be released locally to be effective on endothelial cells [13].
• The other compartment, the 'matrix', has a high acetylcholinesterase activity, and is shown here to have a dense plexus of fibres displaying somatostatin-like immunoreactivity [14].
• However, an ascending cholinergic reticular system has also been postulated to arise from acetylcholinesterase (AChE)-containing neurones in the midbrain and pontine tegmentum [15].

Chemical compound and disease context of Ache

• It is concluded that the cycloheximide pretreatment potentiates DFP toxicity by a mechanism that is related to inhibition of the synthesis of proteins such as AChE, BuChE, and CarbE [16].
• Male Sprague-Dawley rats, injected with the irreversible acetylcholinesterase (AChE) inhibitor soman (pinacolyl methylphosphonofluoridate) 25 micrograms/kg sc, showed no signs of toxicity [17].
• Previous studies have demonstrated that acetylcholinesterase (AChE) promotes the assembly of amyloid-beta-peptides into neurotoxic amyloid fibrils and is toxic for chick retina neuronal cultures and neuroblastoma cells [5].
• We suggest that these modification on cerebral biochemical parameters (Na(+),K(+)-ATPase, acetylcholinesterase and catalase activities) induced by intrastriatal administration of hypoxanthine in all cerebral structures studied, striatum, hippocampus and cerebral cortex, could be involved in the pathophysiology of Lesch-Nyhan disease [18].
• The effects of Huperzine A (HupA), a novel acetylcholinesterase inhibitor, on hydrogen peroxide (H2O2) induced cell lesion, level of lipid peroxidation and antioxidant enzyme activities were investigated in rat pheochromocytoma line PC12 [19].

Biological context of Ache

• For neuroepithelial cells, BChE has been shown to regulate cell division and expression of the postmitotic marker acetylcholinesterase (AChE), while similar studies are lacking for glial cells [20].
• Significant sex differences in the mean AChE activities of normal rats were observed in the superior cervical ganglion (three times more activity in males) and in serum (50% more activity in females) [21].
• Acetylcholinesterase (AChE) activity in the cortex remained inhibited (approximately 29%), whereas in the brainstem there was an increase (approximately 20%) at 1 x LD50 dose of sarin [22].
• Acetylcholinesterase inhibitors: synthesis and structure-activity relationships of omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl derivatives [23].
• Levels of BuChE activity (0.9-1.3 mumol g-1 min-1) were almost unchanged throughout the entire 24-month period, but those of AChE showed a steady and significant increase from 1 to 24 months, remaining relatively high at senescence (4.7 mumol g-1 min-1), when choline uptake had decreased to one-third of its optimal value [24].

Anatomical context of Ache

• Peak inhibition of maternal spinal cord AChE and BuChE activities occurred 2 h and 1 h after dosing, respectively [25].
• Subchronic effects following a single sarin exposure on blood-brain and blood-testes barrier permeability, acetylcholinesterase, and acetylcholine receptors in the central nervous system of rat: a dose-response study [22].
• The acetylcholinesterase activity was measured in erythrocytes and in different brain regions (frontal cortex--FC, pontomedullar area--PM, basal ganglia--BG) [26].
• The concentration of exogenous ACh needed to reduce the spontaneous frequency of contractions of the isolated right atrium by 30, 60, or 90/min fell by 78%, 79% and 84% respectively after BW 284 C51 inhibition of AChE and by 95%, 94% and 94% after simultaneous inhibition of AChE and BuChE [27].
• These results indicate that rat liver expresses several molecular forms of AChE which have multiple interactions with membranes and that liver is unlikely to be the source of the G4 form of BuChE present in high concentration in the plasma [28].

Associations of Ache with chemical compounds

• Homodimeric tacrine congeners as acetylcholinesterase inhibitors [29].
• Extensive in vitro tests of these oximes with acetylcholinesterase inhibited by two different organophosphate agents, echothiophate and diisopropylfluorophosphate, revealed one compound with particularly good reactivation kinetics and affinity for phosphorylated acetylcholinesterase (AChE) [30].
• At 1 1/2 and 24 hr after the DFP treatments, BuChE was considerably more depressed than was the case for AChE [31].
• Main AChE molecular forms of 10.5S (hydrophilic G4H), 9.5S (amphiphilic G4A) and 3.0S (amphiphilic G1A) were identified in retina by subjecting the supernatant S1 to sedimentation analysis in sucrose gradients made with Brij 96 [32].
• The method, which utilizes butyrylthiocholine iodide as the substrate, is a modification of our previously described method for acetylcholinesterase (AChE) histochemistry [33].

Physical interactions of Ache

• By 6 days after transplantation, acetylcholinesterase-positive fibers were observed both on laminin-positive cellular tissue strands connecting the septum and the Schwann cell/extracellular matrix transplants and on the initial portions of the transplants [34].
• Finally, areas of dense [125I]neurotensin labeling often corresponded to zones previously shown to exhibit intense acetylcholinesterase staining, suggesting the existence of a possible link between the expression of neurotensin binding sites and that of acetylcholinesterase in certain neuronal populations [35].
• The distribution of chemically identified neuronal populations was studied in the glomerular layer of the rat olfactory bulb using calcium-binding protein immunocytochemistry combined with acetylcholinesterase histochemistry [36].
• ZMS did not inhibit acetylcholinesterase nor did it occupy the binding sites of muscarinic acetylcholine receptor (M receptor), hence it is neither an cholinesterase inhibitor nor an agonist or antagonist of M receptors [37].
• In vitro studies show that Rb1 has no effect on quinuclidinyl benzylate binding or on acetylcholinesterase activity, but facilitates the release of acetylcholine (ACh) from hippocampal slices [38].

Co-localisations of Ache

• Some VIP-like immunoreactive nerves were shown to be co-localized with acetylcholinesterase-positive cholinergic nerves [39].

Regulatory relationships of Ache

• These data show that the ciliary neurotrophic factor exerts an inhibitory influence on expression of acetylcholinesterase in muscle fibres [40].
• Interleukin-6 and leukemia inhibitory factor promote the survival of acetylcholinesterase-positive neurons in culture from embryonic rat spinal cord [41].
• Thyrotropin-releasing hormone has no influence on the activity of acetylcholinesterase or on choline uptake and release from cerebral synaptosomes [42].
• Esterase activity of endogenous transiently expressed acetylcholinesterase was locally suppressed in visual cortex of infant rats for 2-5 days by the irreversible inhibitor phospholine iodide, delivered from Elvax implants [43].
• The increase of HCl secretion, the decrease of acetylcholinesterase activity and enhanced activity of histidine decarboxylase were observed [44].

Other interactions of Ache

• In Sprague-Dawley rats there were also large individual variations with up to a fivefold range of AChE activities and up to a 100-fold range of BuChE activities in a given tissue [45].
• Ovariectomy increases Na+, K+-ATPase, acetylcholinesterase and catalase in rat hippocampus [46].
• Acute sarin exposure causes differential regulation of choline acetyltransferase, acetylcholinesterase, and acetylcholine receptors in the central nervous system of the rat [47].
• The rough and smooth endoplasmic reticulum and Golgi apparatus were enriched in the G4 molecular form of acetylcholinesterase (AChE) (relative to the G2 molecular form), while the inverse was found in the plasma membrane [28].
• Increased expression of glial fibrillary acidic protein in cerebellum and hippocampus: differential effects on neonatal brain regional acetylcholinesterase following maternal exposure to combined chlorpyrifos and nicotine [48].

Analytical, diagnostic and therapeutic context of Ache

• Effects of hypophysectomy on acetylcholinesterase and butyrylcholinesterase in the rat [21].
• The individual molecular forms (10S and 4S) of maternal and fetal brain AChE and BuChE activities were significantly decreased 1 h after treatment [25].
• Denervation of muscle caused a dramatic reduction in the presence of AchE molecular forms with no discernable influence on the presence of BuchE molecular forms [49].
• Following a single oral administration, both bis(7)-tacrine and tacrine produced dose-dependent inhibitions of AChE in rat brain, but bis(7)-tacrine exhibited higher efficacy and AChE/BChE selectivity than tacrine [50].
• As we report here, we adapted digital scanning densitometry to quantitate AChE histochemical staining in brain sections [51].

References