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

Research output: Contribution to journalArticlepeer-review

Author(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. Sattelle

School/Research organisations

Abstract

A 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.
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Details

Original languageEnglish
Pages (from-to)350-360
Number of pages11
JournalInternational Journal for Parasitology: Drugs and Drug Resistance
Volume8
Issue number2
Early online date4 Jun 2018
DOIs
Publication statusPublished - Aug 2018

    Research areas

  • Glutamate-gated-chloride channel, Tick Ixodes scapularis, Ivermectin, Okaramine B, Acaricide

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