M M Kudelska, A Lewis, C T Ng, D A Doyle, L Holden-Dye, V M O'Connor, R J Walker
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引用次数: 8
Abstract
Caenorhabditis elegans is an informative model to study the neural basis of feeding. A useful paradigm is one in which adult nematodes feed on a bacterial lawn which has been pre-loaded with pharmacological agents and the effect on pharyngeal pumping rate scored. A crucial aspect of this assay is the availability of good quality bacteria to stimulate pumping to maximal levels. A potential confound is the possibility that the pharmacological agent impacts bacterial viability and indirectly influences feeding rate. Here, the actions of nicotine on pharyngeal pumping of C. elegans and on the Escherichia coli bacterial food source were investigated. Nicotine caused an immediate and concentration-dependent inhibition of C. elegans pharyngeal pumping, IC50 4 mM (95% CI = 3.4 mM to 4.8 mM). At concentrations between 5 and 25 mM, nicotine also affected the growth and viability of E. coli lawns. To test whether this food depletion by nicotine caused the reduced pumping, we modified the experimental paradigm. We investigated pharyngeal pumping stimulated by 10 mM 5-HT, a food 'mimic', before testing if nicotine still inhibited this behaviour. The IC50 for nicotine in these assays was 2.9 mM (95% CI = 3.1 mM to 5.1 mM) indicating the depletion of food lawn does not underpin the potency of nicotine at inhibiting feeding. These studies show that the inhibitory effect of nicotine on C. elegans pharyngeal pumping is mediated by a direct effect rather than by its poorly reported bactericidal actions.
秀丽隐杆线虫是研究取食神经基础的信息模型。一个有用的范例是,成年线虫在细菌草坪上进食,细菌草坪已经预先装载了药理学制剂,并对咽泵速率的影响进行了评分。该试验的一个关键方面是优质细菌的可用性,以刺激泵到最大水平。潜在的混淆是药理学制剂可能影响细菌活力并间接影响摄食率。本文研究了尼古丁对秀丽隐杆线虫咽泵和大肠杆菌食物源的影响。尼古丁对秀丽隐杆线虫咽泵产生立即且浓度依赖性的抑制,IC50为4 mM (95% CI = 3.4 mM至4.8 mM)。在浓度为5 ~ 25 mM时,尼古丁对大肠杆菌草坪的生长和活力也有影响。为了检验尼古丁消耗食物是否导致抽吸减少,我们修改了实验范式。在测试尼古丁是否仍然抑制这种行为之前,我们研究了由10毫米5-HT(一种食物“模拟物”)刺激的咽泵。这些试验中尼古丁的IC50值为2.9 mM (95% CI = 3.1 mM至5.1 mM),表明食物草坪的消耗并不支持尼古丁抑制摄食的效力。这些研究表明,尼古丁对秀丽隐杆线虫咽泵的抑制作用是通过直接作用介导的,而不是通过其鲜为人知的杀菌作用介导的。
期刊介绍:
Invertebrate Neurosciences publishes peer-reviewed original articles, reviews and technical reports describing recent advances in the field of invertebrate neuroscience. The journal reports on research that exploits the simplicity and experimental tractability of the invertebrate preparations to underpin fundamental advances in neuroscience. Articles published in Invertebrate Neurosciences serve to highlight properties of signalling in the invertebrate nervous system that may be exploited in the field of antiparisitics, molluscicides and insecticides. Aspects of particular interest include:
Functional analysis of the invertebrate nervous system;
Molecular neuropharmacology and toxicology;
Neurogenetics and genomics;
Functional anatomy;
Neurodevelopment;
Neuronal networks;
Molecular and cellular mechanisms of behavior and behavioural plasticity.