CSIRO Livestock Industries, 306 Carmody Rd., St. Lucia, QLD 4067, Australia.
Int J Parasitol Drugs Drug Resist. 2011 Nov 10;2:29-35. doi: 10.1016/j.ijpddr.2011.10.002. eCollection 2012 Dec.
Macrocyclic lactone (ML) drugs inhibit pharyngeal pumping, motility and egg laying in parasitic nematodes. Previous work has indicated that in vitro effects on worm feeding occurred at lower ivermectin concentrations than effects on worm motility, suggesting that the pharynx musculature was a more important target site for the ML drugs than somatic musculature. We have reassessed this issue of relative sensitivity by examining the response of drug-susceptible and -resistant adult Haemonchus contortus worms to abamectin in vitro using both feeding and motility assays. The motility assay involved observation of changes in the form and degree of movement of individual worms in response to the drug. A comparison of the data from the two assays indicated that worm motility was affected at drug concentrations below those required to inhibit feeding. Analysis of the motility data using different levels of sensitivity (varying in the degree to which they accounted for subtle vs. more profound changes in worm motility) provided an explanation as to why earlier reports had observed feeding to be the more sensitive target. Motility IC50 values shifted from being less than feeding IC50s to being greater than the feeding IC50s as the motility assay analysis method became less sensitive. The present study indicates that when sensitive worm motility assessment methods are utilised, worm motility is affected at lower abamectin concentrations than worm feeding, and hence highlights somatic musculature as a more important target site for this ML drug, and most likely for ML drugs in general.
大环内酯类（ML）药物抑制寄生线虫的咽部抽吸、运动和产卵。以前的工作表明，在体外，伊维菌素对蠕虫摄食的作用发生在比对蠕虫运动作用更低的浓度，这表明咽部肌肉是 ML 药物比体肌更重要的靶位。我们通过使用摄食和运动测定法，重新评估了对药物敏感和耐药的旋毛虫成虫蠕虫对阿维菌素的体外反应，以评估相对敏感性的问题。运动测定法涉及观察个体蠕虫在药物作用下的形态和运动程度的变化。两种测定法的数据比较表明，在抑制摄食所需的药物浓度以下，蠕虫的运动就会受到影响。使用不同的敏感性水平（细微变化和更深刻变化在蠕虫运动中所占的比例不同）对运动数据进行分析，解释了为什么早期的报告观察到摄食是更敏感的靶位。当运动测定法分析方法的敏感性降低时，运动 IC50 值从小于摄食 IC50 值变为大于摄食 IC50 值。本研究表明，当使用敏感的蠕虫运动评估方法时，在较低浓度的阿维菌素下，蠕虫的运动就会受到影响，因此突出了体肌作为该 ML 药物更重要的靶位，并且很可能是一般的 ML 药物。
