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Study of the nematode putative GABA type‐A receptor subunits: evidence for modulation by ivermectin
Author(s) -
Feng XiaoPeng,
Hayashi Jon,
Beech Robin N.,
Prichard Roger K.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01199.x
Subject(s) - biology , receptor , allele , gabaa receptor , ivermectin , xenopus , gamma aminobutyric acid , gaba receptor , genetics , avermectin , gene , microbiology and biotechnology , anatomy , zoology
Two alleles of the HG1 gene, which encodes a putative GABA receptor α/γ subunit, were isolated from Haemonchus contortus . These two alleles were shown previously to be associated with ivermectin susceptibility ( HG1A ) and resistance ( HG1E ), respectively. Sequence analysis indicates that they differ in four amino acids. To explore the functional properties of the two alleles, a full‐length cDNA encoding the β subunit, a key functional component of the GABA receptor, was isolated from Caenorhabditis elegans ( gab‐1 , corresponding to the GenBank locus ZC482.1) and coexpressed in Xenopus oocytes with the HG1 alleles. When gab‐1 was coexpressed with either the HG1A allele or the HG1E allele in Xenopus oocytes, γ‐aminobutyric acid (GABA)‐responsive channels with different sensitivity to the agonist were formed. The effects of ivermectin on the hetero‐oligomeric receptors were determined. Application of ivermectin alone had no effect on the receptors. However, when coapplied with 10 µ m GABA, ivermectin potentiated the GABA‐evoked current of the GAB‐1/HG1A receptor, but attenuated the GABA response of the GAB‐1/HG1E receptor. We demonstrated that the coexpressed HG1 and GAB‐1 receptors are GABA‐responsive, and provide evidence for the possible involvement of GABA receptors in the mechanism of ivermectin resistance.