Wolstenholme Adrian J, Neveu Cedric
Department of Infectious Diseases and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602, U.S.A.
ISP, INRA, Université Tours, UMR1282, Nouzilly 37380, France.
Emerg Top Life Sci. 2017 Dec 22;1(6):667-673. doi: 10.1042/ETLS20170096.
Parasitic nematodes express a large number of distinct nicotinic acetylcholine receptors and these in turn are the targets of many classes of anthelmintic drug. This complexity poses many challenges to the field, including sorting the exact subunit composition of each of the receptor subtypes and how much they vary between species. It is clear that the model organism Caenorhabditis elegans does not recapitulate the complexity of nicotinic pharmacology of many parasite species and data using this system may be misleading when applied to them. The number of different receptors may allow nematodes some plasticity which they can exploit to evolve resistance to a specific cholinergic drug; however, this may mean that combinations of cholinergic agents may be effective at sustainably controlling them. Resistance may involve the expression of truncated receptor subunits that affect the expression levels of the receptors via mechanisms that remain to be deciphered.
寄生线虫表达大量不同的烟碱型乙酰胆碱受体,而这些受体又成为许多类驱虫药物的作用靶点。这种复杂性给该领域带来了诸多挑战,包括确定每种受体亚型的确切亚基组成以及它们在不同物种间的差异程度。很明显,模式生物秀丽隐杆线虫无法概括许多寄生虫物种烟碱药理学的复杂性,使用该系统获得的数据应用于这些寄生虫时可能会产生误导。不同受体的数量可能使线虫具有一定的可塑性,它们可以利用这种可塑性进化出对特定胆碱能药物的抗性;然而,这可能意味着胆碱能药物的组合可能有效地持续控制它们。抗性可能涉及截短的受体亚基的表达,这些亚基通过尚待破解的机制影响受体的表达水平。