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 mil bemycins such as moxidectin (MOX). The importance of this interaction betwe en macrocyclic lactones and GluCls is strengthened by the recent genetic ev idence that GluCls are involved in IVM and MOX resistance in the parasitic nematode Haemonchus contortus (1), We have cloned two full length GluCl put ative alpha-subunit cDNAs from H. contortus (HcGluCla and b) that exhibit d ifferent sized ligand binding domains. Phylogenetic analysis of the conserv ed regions of the amino acid sequence of HcGluCla suggests that it is a mem ber of the GluCl family but forms a distinct subbranch within this family. The expression level of HcGluCla was examined in different developmental st ages of El. contortus (eggs, L3, and adults) and found to be significantly downregulated in eggs compared to adults. (C) 1999 Academic Press.