Nematodes glutamate

Avermectin-sensitive sites in A. mum have been identified on pharyngeal muscle (Martin, 1996) using a two-micropipette current-clamp technique (Fig. 21.13A). Glutamate and avermectins produce hyperpolarization and an increase in Cl conductance when either bath-applied or pressure-ejected on to the pharyngeal preparation (Fig. 21.13B,C). These observations establish that one site of action of the avermectins is the pharyngeal muscle of nematodes and that the avermectins can inhibit feeding in nematodes. 

There is little doubt that milbemycins and avermectins act on chloride channels associated with GABA receptors and amplify GABA functions in the mammalian central nervous system. In the free-living nematode, C elegans, however, avermectin was found to interact with glutamate-gated... 

There are five macrocyclic lactones utilized in veterinary practice of which ivermectin (an aver-mectin) and moxidectin (a milbemycin) are approved for use in the horse. Ivermectin and moxidectin selectively paralyze parasites by increasing muscle chloride permeability through interaction with glutamate-gated chloride ion channels (McKellar Benchaoui 1996). There is evidence that ivermectin and moxidectin may have several sites of action within the parasite and the effects of these compounds may also differ between the nematode species (McKellar Benchaoui 1996, Martin 1997). 

As mentioned, the screening of potent antiparasitic agents using the expression system of the glutamate-gated chloride channel became possible only after the target of AVM was elucidated to be the chloride channels peculiar to nematodes, insects, ticks, etc. [1],... 

For the parasitic nematodes putative neurotransmitters and/or neuromodulators include ACh (excitatory), y-aminobutyric acid (inhibitory), and glutamate (excitatory). Though 5-FIT and the catecholamines are indicated by immuno-cytochemical, biochemical and anatomical techniques, their precise functions as neurosignals remains to be determined. The study of neuropeptides in nematodes has revealed the strong candidacy of the family of FMRFamide-like peptides and in particular the AF peptides which have been shown to have specific physiological effects. 

Glutamate may serve as a neuroactive substance in nematodes, though no satisfactory demonstrations of cellular localization in subsets of neurons have been made. Membrane-associated binding sites for glutamate have been found in C. elegans and H. contortus (157,158). Glutamate binding is inhibited by aspartate and, to a lesser extent, by quisqualate, but not by kainate or N-methyl-o-aspartate (NMDA). 

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