Department of Biology, West Chester University, West Chester, PA 19383, USA.
MedStar Health, Columbia, MD 21044, USA.
Biomolecules. 2024 Sep 18;14(9):1168. doi: 10.3390/biom14091168.
The freshwater planarian is an emerging animal model in neuroscience due to its centralized nervous system that closely parallels closely parallels the nervous system of vertebrates. Cocaine, an abused drug, is the 'founding member' of the local anesthetic family. Parthenolide, a sesquiterpene lactone, acts as a behavioral and physiological antagonist of cocaine in planarians and rats, respectively. Previous work from our laboratory showed that both parthenolide and cocaine reduced planarian motility and that parthenolide reversed the cocaine-induced motility decrease at concentrations where parthenolide does not affect the movement of the worms. However, the exact mechanism of the cocaine/parthenolide antagonism is unknown. Here, we report the results of a Schild analysis to explore the parthenolide/cocaine relationship in the planarian . The Schild slopes of a family of concentration-response curves of parthenolide ± a single concentration of cocaine and vice versa were -0.55 and -0.36, respectively. These slopes were not statistically different from each other. Interestingly, the slope corresponding to the parthenolide ± cocaine (but not the cocaine ± parthenolide) data set was statistically different from -1. Our data suggest an allosteric relationship between cocaine and parthenolide for their effect on planarian motility. To the best of our knowledge, this is the first study about the mechanism of action of the antagonism between cocaine and parthenolide. Further studies are needed to determine the specific nature of the parthenolide/cocaine target(s) in this organism.
淡水涡虫是神经科学中的一种新兴动物模型，因为其中枢神经系统与脊椎动物的神经系统非常相似。可卡因是一种被滥用的药物，是局部麻醉剂家族的“创始成员”。小白菊内酯，一种倍半萜内酯，分别作为可卡因在涡虫和大鼠中的行为和生理拮抗剂。我们实验室的先前工作表明，小白菊内酯和可卡因都降低了涡虫的运动性，而小白菊内酯在不影响蠕虫运动的浓度下逆转了可卡因引起的运动性降低。然而，可卡因/小白菊内酯拮抗的确切机制尚不清楚。在这里，我们报告了一项 Schild 分析的结果，以探讨小白菊内酯/可卡因在涡虫中的关系。小白菊内酯的一组浓度-反应曲线的 Schild 斜率 ± 单一浓度的可卡因和反之亦然分别为-0.55 和-0.36。这些斜率彼此之间没有统计学差异。有趣的是，对应于小白菊内酯±可卡因（但不是可卡因±小白菊内酯）数据集的斜率在统计学上与-1 不同。我们的数据表明，可卡因和小白菊内酯对涡虫运动性的影响之间存在变构关系。据我们所知，这是关于可卡因和小白菊内酯拮抗作用机制的第一项研究。需要进一步研究以确定该生物体中小白菊内酯/可卡因靶标的具体性质。
