Haemonchus contortus: Characterization of a glutamate binding site in unselected and ivermectin-selected larvae and adults

A specific ivermectin-sensitive, glutamate binding site has been identified in the parasitic nematode Haemonchus contortus. Glutamate binding in H. co ntorus was saturable and occurred in a single class of high-affinity bindin g sites which appeared to have pharmacological properties different from th ose of mammalian glutamate receptors. Adult and larval forms of H. contortu s had dramatically different glutamate binding kinetics, the larvae showing nearly up to 200-fold higher B-max values and up to 9-fold increases in K- d values compared to adults. Treatment of adult H, contortus with the anthe lmintic, ivermectin, decreased the B-max value for glutamate binding in the susceptible strain but not in the resistant parasites. Furthermore, select ion for ivermectin resistance was associated with a significant increase in B-max for glutamate binding in adults and a similarly significant increase in glutamate binding affinity in larvae. These results suggest that the H. contortus glutamate binding sire identified in this study may be involved in the phenomenon of ivermectin resistance. (C) 1999 Academic Press.