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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

Furutani, Shogo; Ihara, Makoto; Lees, Kristin; Buckingham, Steven D.; Partridge, Frederick A.; David, Jonathan A.; Patel, Rohit; Warchal, Scott; Mellor, Ian R.; Matsuda, Kazuhiko; Sattelle, David B.

Authors

Shogo Furutani

Makoto Ihara

Kristin Lees

Steven D. Buckingham

Frederick A. Partridge

Jonathan A. David

Rohit Patel

Scott Warchal

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IAN MELLOR IAN.MELLOR@NOTTINGHAM.AC.UK
Assistant Professor

Kazuhiko Matsuda

David B. Sattelle



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.

Citation

Furutani, S., Ihara, M., Lees, K., Buckingham, S. D., Partridge, F. A., David, J. A., …Sattelle, D. B. (2018). The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease. International Journal for Parasitology: Drugs and Drug Resistance, 8(2), 350-360. https://doi.org/10.1016/j.ijpddr.2018.06.001

Journal Article Type Article
Acceptance Date Jun 3, 2018
Online Publication Date Jun 4, 2018
Publication Date Aug 1, 2018
Deposit Date Dec 5, 2018
Publicly Available Date Mar 29, 2024
Journal International Journal for Parasitology: Drugs and Drug Resistance
Print ISSN 2211-3207
Electronic ISSN 2211-3207
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 8
Issue 2
Pages 350-360
DOI https://doi.org/10.1016/j.ijpddr.2018.06.001
Keywords Glutamate-gated chloride channel; Tick Ixodes scapularis; Ivermectin; Okaramine B; Acaricide
Public URL https://nottingham-repository.worktribe.com/output/1163011
Publisher URL https://www.sciencedirect.com/science/article/pii/S2211320717301148?via%3Dihub
Additional Information This article is maintained by: Elsevier; Article Title: The fungal alkaloid Okaramine-B activates an L-glutamate-gated chloride channel from Ixodes scapularis, a tick vector of Lyme disease; Journal Title: International Journal for Parasitology: Drugs and Drug Resistance; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ijpddr.2018.06.001; Content Type: article; Copyright: © 2018 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology.