Distribution and anchoring of molecular forms of acetylcholinesterase

Inestrosa, Nibaldo C.; Perelman, Alejandra

doi:10.1016/0165-6147(89)90067-9

Cited by 53 publications

(25 citation statements)

References 20 publications

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“…AChE is a complex family of molecular forms (13,14). The most common forms are monomers, dimers and tetramers of the same subunit, plus an asymmetric form consisting of three tetramers covalently linked via di sulfide bonds to a three-stranded collagen-like tail.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Acetylcholinesterase-Inhibition by Itopride

Iwanaga

Kimura

Miyashita

et al. 1994

Japanese Journal of Pharmacology

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ABSTRACT-Itopride is a gastroprokinetic benzamide derivative. This agent inhibited both electric eel acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BuChE). The IC50 of itopride with AChE (2.04±0.27 pM) was, however, 100-fold less than that with BuChE, whereas in the case of neostigmine with AChE (11.3±3.4 nM), it was 10-fold less. The recovery of AChE activity inhibited by 10-7 M neostigmine was partial, but that inhibited by upto 3 x 10-5 M itopride was complete when the reaction mix ture was subjected to ultrafiltration. Double reciprocal plots of the experimental data showed that both Km and Vmax were affected by itopride, suggesting that the inhibition is a "mixed" type, although primarily being an uncompetitive one. The inhibitory effect of itopride on cholinesterase (ChE) activity in guinea pig gastrointestine was much weaker than that on pure AChE. However, in the presence of a low dose of diisopropyl fluorophosphate, just enough to inhibit BuChE but not AChE, the IC50s of itopride against ChE activities were found to be about 0.5 1tM. In conclusion, itopride exerts reversible and a "mixed" type of inhibition preferably against AChE. The IC50 of itopride for electric eel and guinea pig gastrointestinal AChE inhibition was 200 times and 50 times as large as that of neostigmine, respectively.

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Section: Discussionmentioning

confidence: 99%

Characterization of Acetylcholinesterase-Inhibition by Itopride

Iwanaga

Kimura

Miyashita

et al. 1994

Japanese Journal of Pharmacology

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“…[11][12][13][14] Several studies on brains displaying AD lesions have shown changes in the expression and distribution of acetylcholinesterase (AChE), the enzyme responsible for the hydrolysis of the neurotransmitter acetylcholine. [15][16][17] Firstly, AChE activity is lost in specific regions of the AD brain, such as the cortex, hippocampus, amygdala and nucleus basalis of Meynert. 2,18,19 Secondly, it was shown that transgenic mice overexpressing human AChE in brain neurons underwent progressive cognitive deterioration.…”

Section: Introductionmentioning

confidence: 99%

Toxic effects of acetylcholinesterase on neuronal and glial-like cells in vitro

et al. 1998

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Acetylcholinesterase (AChE), the enzyme involved in the hydrolysis of the neurotransmitter acetylcholine, has been implicated in non-cholinergic actions which may play a role in neurodegenerative diseases such as Alzheimer's disease. To study the potential cytotoxicity of brain AChE, the effects of affinity purified AChE were analyzed on neuronal (Neuro 2a) and glial-like (B12) cells. LDH release and MTT reduction assays showed that AChE was toxic; the toxicity was dependent on the enzyme concentration, time of incubation and cellular density. The toxic effect of AChE was not related to its catalytic activity, since the anti-cholinesterase drug BW284C51 and heat inactivation were unable to block the effects of the enzyme. When cells were incubated at 4؇C, toxicity was completely blocked, in contrast to cells incubated at 37؇C. The presence of serum in the culture medium inhibited the toxic effects of AChE. Cytoplasmic shrinkage, condensation and fragmentation of nucleus as well as DNA strand breaks detected with the TUNEL technique indicated that apoptotic cell death is involved in the effect of AChE. Considering that we have previously shown that AChE promotes the assembly of ␤-amyloid peptide into neurotoxic amyloid fibrils, it is conceivable that the neurotoxicity of AChE shown here may play a role in the neuronal degeneration observed in Alzheimer's disease.

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“…The rest of the AChE activity in this fraction is probably localized within intact microsomes and is not, therefore, accessible to PIPLC. In the crude granular fraction, which contains the chromaffin vesicles, only a very small amount of the total AChE activity was released by PIPLC, as might be expected since most of the AChE activity in the chromaffin granules corresponds to the G4 form of the enzyme (Inestrosa et al, 1989), which has been shown, in other tissues, to be anchored by a different type of anchor than the dimer (Inestrosa et al, 1987b;.…”

Section: Discussionmentioning

confidence: 89%

Phosphatidylinositol‐specific phospholipase C solubilized G₂ acetylcholinesterase from plasma membranes of chromaffin cells

Prieto

Fuentes

Arqueros

et al. 1989

J of Neuroscience Research

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Using whole homogenates and defined subcellular fractions of bovine adrenal medulla, we investigated the properties of the dimeric G2 molecular form of acetylcholinesterase (AChE), its distribution, and the mode of attachment to chromaffin cells. Our studies indicate that a substantial fraction of the G2 form is specifically susceptible to solubilization by phosphatidylinositol-specific phospholipase C (PIPLC) from subcellular fractions enriched with plasma membrane fragments. The results suggest that the G2 form of AChE is anchored in the plasma membrane to a glycolipid domain that contains phosphatidylinositol. Since a Ca+2-dependent PIPLC has been previously described in chromaffin granules, it is possible that the adrenal AChE could be released by a system reminiscent of that involved in the case of the surface glycoprotein of Trypanosoma brucei.

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Distribution and anchoring of molecular forms of acetylcholinesterase

Cited by 53 publications

References 20 publications

Characterization of Acetylcholinesterase-Inhibition by Itopride

Characterization of Acetylcholinesterase-Inhibition by Itopride

Toxic effects of acetylcholinesterase on neuronal and glial-like cells in vitro

Phosphatidylinositol‐specific phospholipase C solubilized G₂ acetylcholinesterase from plasma membranes of chromaffin cells

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Distribution and anchoring of molecular forms of acetylcholinesterase

Cited by 53 publications

References 20 publications

Characterization of Acetylcholinesterase-Inhibition by Itopride

Characterization of Acetylcholinesterase-Inhibition by Itopride

Toxic effects of acetylcholinesterase on neuronal and glial-like cells in vitro

Phosphatidylinositol‐specific phospholipase C solubilized G2 acetylcholinesterase from plasma membranes of chromaffin cells

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Phosphatidylinositol‐specific phospholipase C solubilized G₂ acetylcholinesterase from plasma membranes of chromaffin cells