Acetyicholinesterase secretion–a parameter for the interpretation of <i>in vitro</i> anthelmintic screens

Rapson, E. B.; Chilwan, A. S.; Jenkins, D. C.

doi:10.1017/s0031182000064180

Cited by 18 publications

(12 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It can be used as a parameter for detecting new antiparasitic agents (Rapson et al 1986(Rapson et al , 1987Alonso-Villalobos and Martı´nez-Grueiro 2000) . When comparing in vitro effects of the tested compounds it appears that the secretion of AChE is a much more sensitive test than the release of AcP.…”

Section: Discussionmentioning

confidence: 99%

Nematocidal activity of nitazoxanide in laboratory models

Fonseca-Salamanca

Martı́nez-Grueiro

Martínez-Fernández

2003

Parasitology Research

View full text Add to dashboard Cite

The nematocidal activity of a broad-spectrum antiparasitic agent, nitazoxanide [( N-(5-nitrothiazol-2-gammal)salicylamide; NTZ], was evaluated in both in vitro and in vivo models using Caenorhabditis elegans, Heligmosomoides polygyrus and Trichinella spiralis. In vitro, NTZ (100 muM) exhibited a low activity against C. elegans and had no effect on embryonation and hatching of H. polygyrus eggs. At concentrations of 100 and 50 muM, the inhibition of excretion/secretion of acetylcholinesterase and acid phosphatase of adult H. polygyrus by NTZ was variable. The in vitro effects of mebendazole (5 muM), albendazole (1 muM) and levamisole (10 muM) were superior to those of NTZ. In mice, NTZ at 1 g/kg proved to be inactive against preadults of T. spiralis whereas mebendazole at 10 mg/kg reduced the worm burden by up to 83%. NTZ at 1 g/kg per day for 3 consecutive days showed a low activity against adults of H. polygyrus (21% reduction). Levamisole, at a single dose of 10 mg/kg, reduced the worm burden by up to 89.9%. The results of this study suggest that NTZ would not have met criteria of a candidate compound.

show abstract

Section: Discussionmentioning

confidence: 99%

Nematocidal activity of nitazoxanide in laboratory models

Fonseca-Salamanca

Martı́nez-Grueiro

Martínez-Fernández

2003

Parasitology Research

View full text Add to dashboard Cite

show abstract

“…Adult stages of other nematodes also secrete AChE (Ogilvie et al, 1973) and they could be used for the screening of anthelmintics in vitro by employing this biochemical parameter (Rapson et al, 1986;Mallet and Kerboeuf, 1993).…”

Section: Introductionmentioning

confidence: 99%

The In Vitro Secretion of Acetylcholinesterase by Adult Stages of Heligmosomoides polygyrus: the Effects of Broad‐Spectrum Anthelmintics

Alonso-Villalobos

Martínez-Grueiro²

2000

Journal of Veterinary Medicine, Series B

View full text Add to dashboard Cite

The secretion of acetylcholinesterase (AChE) by female and male Heligmosomoides polygyrus was studied in different in vitro culture media. AChE secretion was increased in the presence of fetal calf serum or bovine serum albumin (BSA). In the absence of crowding effects, specific AChE activity in excretion/secretion products was higher for male (2.41 +/- 0.07 mumol min-1 l-1 mg-1) than for female (0.56 +/- 0.04 mumol min-1 mg-1) worms but on a per nematode basis both sexes showed comparable rates of secretion. Acetylthiocholine iodide was the favoured substrate of the enzyme. When the nematodes were incubated in vitro with albendazole (ABZ), ricobendazole (RBZ), mebendazole (MBZ), levamisole (LVM), morantel (MRT) or ivermectin (IVM), at concentrations from 1 mM to 10 nM, in RPMI medium for 2 or 6 h and then transferred to a drug-free medium (RPMI medium supplemented with 0.5% BSA) for 24 h or continuously exposed to the drugs in supplement-free medium (24 h), the concentration- and time-dependent inhibitory effects on AChE secretion were observed. The continued exposure to the drugs for all incubation periods (with a single exception for LVM 1 mM) produced the highest levels of inhibition. Under these conditions, the concentrations inhibiting the secretion of AChE by 50% (IC50) relative to drug-free controls were estimated. The IC50 values ranged from 0.012 microM (IVM) to 2.96 microM (MRT). The potential of this bioassay for the selective primary evaluation of new compounds with broad-spectrum anti-nematodal activity is discussed.

show abstract

“…; Rapson et al . ). The discovery of AChE proteins secreted by Nippostrongylus brasiliensis and Dictyocaulus viviparus , with characteristic sequence differences from the canonical neuronal AChE were the first demonstration of AChE gene amplification in nematodes beyond the 3‐4 genes encoding neuronal enzymes (Hussein et al .…”

Section: Amplification Of Ache Genes In Parasitic Nematodesmentioning

confidence: 97%

Natural genomic amplification of cholinesterase genes in animals

Chatonnet

Lenfant

Marchot

et al. 2017

Journal of Neurochemistry

View full text Add to dashboard Cite

Tight control of the concentration of acetylcholine at cholinergic synapses requires precise regulation of the number and state of the acetylcholine receptors, and of the synthesis and degradation of the neurotransmitter. In particular, the cholinesterase activity has to be controlled exquisitely. In the genome of the first experimental models used (man, mouse, zebrafish and drosophila), there are only one or two genes coding for cholinesterases, whereas there are more genes for their closest relatives the carboxylesterases. Natural amplification of cholinesterase genes was first found to occur in some cancer cells and in insect species subjected to evolutionary pressure by insecticides. Analysis of the complete genome sequences of numerous representatives of the various metazoan phyla show that moderate amplification of cholinesterase genes is not uncommon in molluscs, echinoderms, hemichordates, prochordates or lepidosauria. Amplification of acetylcholinesterase genes is also a feature of parasitic nematodes or ticks. In these parasites, over-production of cholinesterase-like proteins in secreted products and the saliva are presumed to have effector roles related to host infection. These amplification events raise questions about the role of the amplified gene products, and the adaptation processes necessary to preserve efficient cholinergic transmission.

show abstract

Acetyicholinesterase secretion–a parameter for the interpretation of in vitro anthelmintic screens

Cited by 18 publications

References 9 publications

Nematocidal activity of nitazoxanide in laboratory models

Nematocidal activity of nitazoxanide in laboratory models

The In Vitro Secretion of Acetylcholinesterase by Adult Stages of Heligmosomoides polygyrus: the Effects of Broad‐Spectrum Anthelmintics

Natural genomic amplification of cholinesterase genes in animals

Contact Info

Product

Resources

About