AChE activity

The primary site of action of OPs is AChE, with which they interact as suicide substrates (see also Section 10.2.2 and Chapter 2, Figure 2.9). Similar to other B-type esterases, AChE has a reactive serine residue located at its active site, and the serine hydroxyl is phosphorylated by organophosphates. Phosphorylation causes loss of AChE activity and, at best, the phosphorylated enzyme reactivates only slowly. The rate of reactivation of the phosphorylated enzyme depends on the nature of the X groups, being relatively rapid with methoxy groups (tso 1-2 h), but slower with larger... 

Since ACh appears to be important in memory processing and as its concentration is significantly reduced in appropriate brain areas in AzD then augmenting its action should at least improve memory function. ACh activity may be increased by... 

EEG slow waves. The differential EEG and ACh responses to dialysis delivery of AF-DX 116 (M2/M4) versus pirenzepine (M1/M4) supports the conclusion that, in B6 mouse, postsynaptic muscarinic receptors of the Ml subtype form one receptor mechanism by which ACh activates the EEG (Douglas et al, 2002a). The data summarized in Fig. 5.11 provide direct measures of G protein activation in basal forebrain and prefrontal cortex by muscarinic cholinergic receptors (DeMarco et al, 2004). The in vitro data of Fig. 5.11A indicate the presence of functional muscarinic receptors in regions of B6 mouse prefrontal cortex where in vivo microdialysis studies (Douglas et al, 2002a, b) revealed modulation of ACh release and EEG by pre- and postsynaptic muscarinic receptors (Figs. 5.9 and 5.10). 

One unit of AChE activity is defined as 1 jimol of substrate hydrolysed min-1 at 37°C. nd = not detectable. 

Fig. 11.1. Somatic and secreted AChEs in N. brasiliensis. Extracts of parasites collected 4 days (track 1) and 8 days (track 3) post-infection of rats were resolved by non-denaturing PAGE alongside secreted products from parasites also collected 4 days (track 2) and 8 days (track 4) postinfection, and AChE activity visualized by cytochemical staining. Secretory enzymes designated as forms A, B and C are indicated, and the non-secreted isoform is arrowed. Reproduced from Hussein etal. (1999b), with permission.

Principle Biosensors consist of paper matrixes and tissue enzyme preparations, often the pure enzyme AChE or AChE-containing cells. As seen in Fig.l, main scheme of the preparation technology and procedure includes (i) the preparation of same kinds of biotests-biosensors, which are paper matrixes impregnated with tissue preparation of AChE and covered by polymer film. (ii) biochemical reactions of the AChE activity with and without inhibitors tested and (iii) the photometric analysis of the samples for quantitative estimation of the biochemical reactions. 

Kitten, 3 months old, died in 6 h following hypersalivation, ataxia, depression, and seizures. No histopathology at necropsy brain AChE activity normal. Fenvalerate residues, in pg/kg, were 345,000 in skin, 230 in kidney, 150 in liver, 10 in brain. Adult (4-year-old) showed signs of toxicosis 4 h after topical application by 30 h, animal had lowered body temperature, bradycardia, and other signs of fenvalerate poisoning. At death, shortly thereafter, fenvalerate residues were 1000 pg/kg in skin and 20 pg/kg in liver... 

In most cases, the appearance of first cholinergic signs and symptoms is observed at the time when AChE activity in blood is reduced down to 50%. It is generally recognized that the inhibition of AChE and ChE activities in human blood by 75% is an indicator of danger and requires taking immediate measures to discontinue the exposure. 

A reduction of the mediator concentration in synapses can be also achieved by the AChE activation, inhibition of mediator release into synaptic slit, slowing-down of reverse choline intake, as well as by using AChE compounds [5],... 

Medication Means of Increasing Acetylcholine (ACh) Activity Clinical Uses... 

In the following example we describe the implementation of a mass spectromet-ric assay for acetylcholinesterase (AChE) [22]. AChE plays an important role in the nervous system. This enzyme rapidly hydrolyzes the active neurotransmitter acetylcholine into the inactive compounds choline and acetic acid. Amongst others, low levels of acetylcholine in the synaptic cleft are associated with Alzheimer s disease [23, 24]. Patients afflicted by this disease may benefit from inhibition of AChE activity thereby increasing ACh level. 

Of the many types of phenolic compounds, not many have been shown to possess AChE inhibitory activity. The root and stem bark of Magnolia officinalis Rehd. Et Wils. contains the biphenolic lignans, honokiol (72) and magnolol (73). Both lignans increased ChAT activity and inhibited AChE activity in vitro, and increased hippocampal ACh release in vivo) These two compounds also appeared to have antioxidant antiinflammatory... 

As an example of the use of these tracers in drug development, [ C]MP4A has been used to study the regional effects of donepezil and rivastigmine on cortical AChE activity in patients with AD [66], Both drugs were found to reduce... 

AChE activity to a greater extent in the frontal cortex compared with the temporal cortex. Similar effects on brain AChE activity were found after 3 months of treatment with donepezil (10mg/day) or after 3-5 months of treatment with rivastigmine (9 mg/day) [66],... 

Bocquene, G., Galgani, E., Truquet, P. (1990). Characterisation and assay conditions for use of AChE activity from several marine species in pollution monitoring. Marine Environmental Research, 30 75-89. 

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