Nicotinic acetylcholine receptors: A comparison of the nAChRs of Caenorhabditis elegans and parasitic nematodes

• Published in: Parasitology international Vol. 62; no. 6; pp. 606 - 615
• Main Authors: Holden-Dye, Lindy, Joyner, Michelle, O'Connor, Vincent, Walker, Robert J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 01.12.2013
• Subjects: Animals; Anthelmintic; anthelmintics; Anthelmintics - pharmacology; Ascariasis - parasitology; Ascaris suum; Ascaris suum - drug effects; Ascaris suum - genetics; Ascaris suum - metabolism; Caenorhabditis elegans; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; cholinergic receptors; free-living nematodes; Gastroenterology and Hepatology; Gene Expression; genes; Haemonchiasis - parasitology; Haemonchus - drug effects; Haemonchus - genetics; Haemonchus - metabolism; Haemonchus contortus; Helminth Proteins - drug effects; Helminth Proteins - genetics; Helminth Proteins - metabolism; Infectious Disease; Levamisole; Levamisole - pharmacology; nAChRs; Nematoda; Nicotine; Oocytes; parasitology; pharmacology; physiology; Protein Subunits - genetics; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - genetics; Receptors, Nicotinic - metabolism; Xenopus laevis; nAChRs; Caenorhabditis elegans; Haemonchus contortus; Anthelmintic; Levamisole; Ascaris suum; Nicotine
• ISSN: 1383-5769; 1873-0329; 1873-0329
• DOI: 10.1016/j.parint.2013.03.004

Nicotinic acetylcholine receptors (nAChRs) play a key role in the normal physiology of nematodes and provide an established target site for anthelmintics. The free-living nematode, Caenorhabditis elegans, has a large number of nAChR subunit genes in its genome and so provides an experimental model for testing novel anthelmintics which act at these sites. However, many parasitic nematodes lack specific genes present in C. elegans, and so care is required in extrapolating from studies using C. elegans to the situation in other nematodes. In this review the properties of C. elegans nAChRs are reviewed and compared to those of parasitic nematodes. This forms the basis for a discussion of the possible subunit composition of nAChRs from different species of parasitic nematodes. Currently our knowledge on this is largely based on studies using heterologous expression and pharmacological analysis of receptor subunits in Xenopus laevis oocytes. It is concluded that more information is required regarding the subunit composition and pharmacology of endogenous nAChRs in parasitic nematodes. [Display omitted] •C. elegans nAChRs are reviewed and compared to those of parasitic nematodes.•The stoichiometry of nAChRs from C. elegans and parasitic nematodes is discussed.•Differences between nAChRs from C. elegans and parasitic nematodes are highlighted.•More information is required for nAChRs in parasitic nematodes.•The potential for resistance-breaking anthelmintics is evaluated.