The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease

Publication date: August 2018Source: International Journal for Parasitology: Drugs and Drug Resistance, Volume 8, Issue 2Author(s): Shogo Furutani, Makoto Ihara, Kristin Lees, Steven D. Buckingham, Frederick A. Partridge, Jonathan A. David, Rohit Patel, Scott Warchal, Ian R. Mellor, Kazuhiko Matsuda, David B. SattelleAbstractA novel L-glutamate-gated anion channel (IscaGluCl1) has been cloned from the black-legged tick, Ixodes scapularis, which transmits multiple pathogens including the agents of Lyme disease and human granulocytic anaplasmosis. When mRNA encoding IscaGluCl1 was expressed in Xenopus laevis oocytes, we detected robust 50–400 nA currents in response to 100 μM L-glutamate. Responses to L-glutamate were concentration-dependent (pEC50 3.64 ± 0.11). Ibotenate was a partial agonist on IscaGluCl1. We detected no response to 100 μM aspartate, quisqualate, kainate, AMPA or NMDA. Ivermectin at 1 μM activated IscaGluCl1, whereas picrotoxinin (pIC50 6.20 ± 0.04) and the phenylpyrazole fipronil (pIC50 6.90 ± 0.04) showed concentration-dependent block of the L-glutamate response. The indole alkaloid okaramine B, isolated from fermentation products of Penicillium simplicissimum (strain AK40) grown on okara pulp, activated IscaGluCl1 in a concentration-dependent manner (pEC50 5.43 ± 0.43) and may serve as a candidate lead compound for the development of new acaricides.Graphical abstract
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research

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Source: Clinical Medicine and Research - Category: General Medicine Authors: Tags: Clin Med Res Source Type: research
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Source: WBZ-TV - Breaking News, Weather and Sports for Boston, Worcester and New Hampshire - Category: Consumer Health News Authors: Tags: Boston News Health Syndicated CBSN Boston Deer Ticks LYME DISEASE Maine news Source Type: news
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Source: Ticks and Tick borne Diseases - Category: Zoology Source Type: research
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Source: Ticks and Tick borne Diseases - Category: Zoology Source Type: research
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Source: The Journal of Parasitology - Category: Parasitology Authors: Tags: J Parasitol Source Type: research
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Source: WBZ-TV - Breaking News, Weather and Sports for Boston, Worcester and New Hampshire - Category: Consumer Health News Authors: Tags: Boston News Health Syndicated CBSN Boston LYME DISEASE Maine news ticks Source Type: news
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Source: Annals of Agricultural and Environmental Medicine : AAEM - Category: Environmental Health Authors: Tags: Ann Agric Environ Med Source Type: research
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Source: Ticks and Tick borne Diseases - Category: Zoology Source Type: research
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Source: Acta Veterinaria Hungarica - Category: Veterinary Research Authors: Tags: Acta Vet Hung Source Type: research
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