Abstract
Natural plant compounds, such as betaine, are described to have nematocidal properties. Betaine also acts as a neurotransmitter in the free-living model nematode Caenorhabditis elegans, where it is required for normal motility. Worm motility is mediated by nicotinic acetylcholine receptors (nAChRs), including subunits from the nematode-specific DEG-3 group. Not all types of nAChRs in this group are associated with motility, and one of these is the DEG-3/DES-2 channel from C. elegans, which is involved in nociception and possibly chemotaxis. Interestingly, the activity of DEG-3/DES-2 channel from the parasitic nematode of ruminants, Haemonchus contortus, is modulated by monepantel and its sulfone metabolite, which belong to the amino-acetonitrile derivative anthelmintic drug class. Here, our aim was to advance the pharmacological knowledge of the DEG-3/DES-2 channel from C. elegans by functionally expressing the DEG-3/DES-2 channel in Xenopus laevis oocytes and using two-electrode voltage-clamp electrophysiology. We found that the DEG-3/DES-2 channel was more sensitive to betaine than ACh and choline, but insensitive to monepantel and monepantel sulfone when used as direct agonists and as allosteric modulators in co-application with betaine. These findings provide important insight into the pharmacology of DEG-3/DES-2 from C. elegans and highlight the pharmacological differences between non-parasitic and parasitic nematode species.
Highlights
Parasitic nematodes of crops, livestock, companion animals and humans have long been a major burden as they cause losses of food, morbidity and mortality in animals and humans
In the free-living model nematode Caenorhabditis elegans, betaine acts as a neurotransmitter, and is required for a basal level of motility shown to be mediated by the ACR-23 nicotinic acetylcholine choline receptor [10]
Our results show that the Cel-DEG-3/DES-2 channel is highly sensitive to betaine, but insensitive to monepantel and monepantel sulfone both as agonists and allosteric modulators
Summary
Livestock, companion animals and humans have long been a major burden as they cause losses of food, morbidity and mortality in animals and humans. In the free-living model nematode Caenorhabditis elegans, betaine acts as a neurotransmitter, and is required for a basal level of motility shown to be mediated by the ACR-23 nicotinic acetylcholine choline receptor (nAChR) [10]. These nAChRs are pentameric proteins that are either homomeric- or heteromeric ligand-gated ion channels of the Cys-loop family, and are expressed in neuronal-, non-neuronal and muscle cell membranes [11,12]. The action of AADs on Cel-DEG-3/DES-2 has not yet been assayed
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