Haemopoiesis

Wolstenholme, G. E. W.; OʼConnor, Maeve; Rogers, Blair O.

doi:10.1097/00000658-196203000-00019

Cited by 3 publications

(3 citation statements)

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“…Other anthelmintic drug classes also affect locomotion: the macrocyclic lactones (ivermectin) produce paralysis of the body-wall muscle (Wolstenholme and Rogers, 2005;Kotze et al 2004); piperazine inhibits body muscle as a GABA agonist (Martin, 1982); emodepside inhibits muscle, apparently increasing a Slo-1 potassium current (Guest et al 2007). Even benzimidazoles, which bind β-tubulin, affect larval motility (Kotze et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Microfluidic bioassay to characterize parasitic nematode phenotype and anthelmintic resistance

et al. 2010

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SUMMARYWith increasing resistance to anti-parasitic drugs, it has become more important to detect and recognize phenotypes of resistant isolates. Molecular methods of detecting resistant isolates are limited at present. Here, we introduce a microfluidic bioassay to measure phenotype using parameters of nematode locomotion. We illustrate the technique on larvae of an animal parasite Oesophagostomum dentatum. Parameters of sinusoidal motion such as propagation velocity, wavelength, wave amplitude, and oscillation frequency depended on the levamisole-sensitivity of the isolate of parasitic nematode. The levamisole-sensitive isolate (SENS) had a mean wave amplitude of 135 μm, which was larger than 123 μm of the levamisole-resistant isolate (LEVR). SENS had a mean wavelength of 373 μm, which was less than 393 μm of LEVR. The mean propagation velocity of SENS, 149 μm s −1 , was similar to LEVR, 143 μm s −1 . The propagation velocity of the isolates was inhibited by levamisole in a concentration-dependent manner above 0.5 μM. The EC 50 for SENS was 3 μM and the EC 50 for LEVR was 10 μM. This microfluidic technology advances present-day nematode migration assays and provides a better quantification and increased drug sensitivity. It is anticipated that the bioassay will facilitate study of resistance to other anthelmintic drugs that affect locomotion.

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Section: Discussionmentioning

confidence: 99%

Microfluidic bioassay to characterize parasitic nematode phenotype and anthelmintic resistance

et al. 2010

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“…The evidence implicating the LGCC, especially glutamate-gated chloride channels (GluCl), as the main target of the ML has been extensively reviewed and will not be repeated here (Wolstenholme and Rogers, 2005). However, it is clear that avermectins can interact with a variety of different channels in addition to the GluCl, including nematode and mammalian GABA A and glycine receptors (Adelsberger, Lepier and Dudel, 2000 ;Dawson et al 2000 ;Shan, Haddrill and Lynch, 2001), a7 nicotinic acetylcholine receptors and P2X 4 receptors (Krause et al 1998 ;Khakh et al 1999).…”

Section: R I T E R I a F O R E S T A B L I S H I N G A P O L Y M O mentioning

confidence: 99%

Nematode ligand-gated chloride channels: an appraisal of their involvement in macrocyclic lactone resistance and prospects for developing molecular markers

2007

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SUMMARYLigand-gated chloride channels, including the glutamate-(GluCl) and GABA-gated channels, are the targets of the macrocyclic lactone (ML) family of anthelmintics. Changes in the sequence and expression of these channels can cause resistance to the ML in laboratory models, such as Caenorhabditis elegans and Drosophila melanogaster. Mutations in multiple GluCl subunit genes are required for high-level ML resistance in C. elegans, and this can be influenced by additional mutations in gap junction and amphid genes. Parasitic nematodes have a different complement of channel subunit genes from C. elegans, but a few genes, including avr-14, are widely present. A polymorphism in an avr-14 orthologue, which makes the subunit less sensitive to ivermectin and glutamate, has been identified in Cooperia oncophora, and polymorphisms in several subunits have been reported from resistant isolates of Haemonchus contortus. This has led to suggestions that ML resistance may be polygenic. Possible reasons for this, and its consequences for the development of molecular tests for resistance, are explored.

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“…Investigations into the function of LGCC subunits in parasitic nematodes have emerged largely through studies of the mode of action of the anti-parasitic drug ivermectin (Wolstenholme and Rogers, 2005). Research in this area has lead to the identification and characterization of several ivermectin receptors, specifically GluCls, from various parasitic nematodes, including Haemonchus contortus (=the barber's pole worm of small ruminants), Cooperia oncophora, Cylicocyclus nassatus, Ascaris suum and Dirofilaria immitis (see Delany et al 1998 ;Forrester et al 1999 ;Jagannathan et al 1999 ;Njue et al 2004 ;Yates and Wolstenholme, 2004 b;Tandon et al 2006).…”

Section: Introductionmentioning

confidence: 99%

A novel member of the ligand-gated chloride channel gene family from Haemonchus contortus

Forrester

Siddiqui

2007

Parasitology

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Ligand-gated chloride channels (LGCCs) are key components of the nervous system of parasitic nematodes and important targets for anthelmintics. Here, we describe the isolation and characterization of a novel member of the LGCC gene family (HcLGCC1) from the parasitic nematode Haemonchus contortus. Sequence analysis revealed that the channel subunit encoded by HcLGCC1 is anion selective and a member of a group of channels characterized as having two Cys-loops in the N-terminal ligand-binding domain. Although the overall function of HcLGCC1 is presently unknown, the gene may play a key role in the early developmental stages of the parasite. Further investigations into the function of LGCCs, such as HcLGCC1, in parasitic nematodes should have implications for the discovery of new anthelmintic targets.

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Haemopoiesis

Cited by 3 publications

References 0 publications

Microfluidic bioassay to characterize parasitic nematode phenotype and anthelmintic resistance

Microfluidic bioassay to characterize parasitic nematode phenotype and anthelmintic resistance

Nematode ligand-gated chloride channels: an appraisal of their involvement in macrocyclic lactone resistance and prospects for developing molecular markers

A novel member of the ligand-gated chloride channel gene family from Haemonchus contortus

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