Cloning, sequencing, and developmental expression levels of a novel glutamate-gated chloride channel homologue in the parasitic nematode Haemonchus contortus

Glutamate-gated chloride channels (GluCls) are the proposed site of action for macrocyclic lactone anthelminthics such as ivermectin (IVM) and the milbemycins such as moxidectin (MOX). The importance of this interaction between macrocyclic lactones and GluCls is strengthened by the recent genetic evidence that GluCls are involved in IVM and MOX resistance in the parasitic nematode Haemonchus contortus (1), We have cloned two full length GluCl putative alpha-subunit cDNAs from H. contortus (HcGluCla and b) that exhibit different sized ligand binding domains. Phylogenetic analysis of the conserved regions of the amino acid sequence of HcGluCla suggests that it is a member of the GluCl family but forms a distinct subbranch within this family. The expression level of HcGluCla was examined in different developmental stages of El. contortus (eggs, L3, and adults) and found to be significantly downregulated in eggs compared to adults. (C) 1999 Academic Press.