Nematode neuromuscular nicotinic acetylcholine receptor (nAChR)

Nematode neuromuscular nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that play a critical role in the excitatory neurotransmission of parasitic and free-living roundworms (Martin et al., 2012). These receptors are located on the body wall muscle cells and are composed of various alpha and non-alpha subunits, such as UNC-38, UNC-29, and UNC-63, which assemble to form a cation-selective pore (Holden-Dye & Walker, 2014). Upon binding of the neurotransmitter acetylcholine, the channel opens to allow the influx of sodium and calcium ions, leading to muscle depolarization and contraction (Abongwa et al., 2017). In veterinary and human medicine, these receptors are the primary targets for several major classes of anthelmintic drugs, including imidazothiazoles like levamisole and tetrahydropyrimidines like pyrantel. These therapeutic agents generally act as potent agonists that induce prolonged activation of the receptor, resulting in spastic paralysis and the subsequent expulsion of the worm from the host (Martin & Robertson, 2007). Conversely, newer drugs like derquantel function as antagonists, leading to flaccid paralysis. The structural diversity of these receptors across different species allows for selective toxicity against parasites, although the emergence of resistance through genetic mutations in receptor subunits remains a significant challenge in treating helminth infections (Beech et al., 2013).

Other names

Nematode nAChRLevamisole-sensitive receptorL-type nAChRN-type nAChRNicotine-sensitive receptorAcetylcholine-gated cation channel

Anthelmintic drugs typically act as agonists (e.g., levamisole) causing persistent depolarization and spastic paralysis, or as antagonists (e.g., derquantel) causing flaccid paralysis of the nematode body wall muscle.