Campus Units

Biomedical Sciences, Entomology

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

12-30-2018

Journal or Book Title

International Journal for Parasitology: Drugs and Drug Resistance

DOI

10.1016/j.ijpddr.2018.12.005

Abstract

The ongoing and widespread emergence of resistance to the existing anti-nematodal pharmacopeia has made it imperative to develop new anthelminthic agents. Historically, plants have been important sources of therapeutic compounds and offer an alternative to synthetic drugs. Monoterpenoids are phytochemicals that have been shown to produce acute toxic effects in insects and nematodes. Previous studies have shown nicotinic acetylcholine receptors (nAChRs) to be possible targets for naturally occurring plant metabolites such as carvacrol and carveol. In this study we examined the effects of monoterpenoid compounds on a levamisole sensitive nAChR from Oesophagostomum dentatum and a nicotine sensitive nAChR from Ascaris suum. We expressed the receptors in Xenopus laevis oocytes and used two-electrode voltage-clamp to characterize the effect of various compounds on these cys-loop receptors. At 100 μM the majority of these compounds acted as antagonists. Interestingly, further experiments revealed that both 0.1 μM and 10 μM menthol potentiated acetylcholine and levamisole responses in the levamisole sensitive receptor but not the nicotine sensitive receptor. We also investigated the effects of 0.1 μM menthol on the contractility of A. suum somatic muscle strips. Menthol produced significant potentiation of peak contractions at each concentration of acetylcholine. The positive allosteric modulatory effects of menthol in both in vivo and in vitro experiments suggests menthol as a promising candidate for combination therapy with cholinergic anthelmintics.

Comments

This is a manuscript of an article published as Choudhary, Shivani, Djordje S. Marjianović, Colin R. Wong, Xiaoyu Zhang, Melanie Abongwa, Joel R. Coats, Saša M. Trailović, Richard J. Martin, and Alan P. Robertson. "Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors." International Journal for Parasitology: Drugs and Drug Resistance (2018). doi: 10.1016/j.ijpddr.2018.12.005.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Copyright Owner

Australian Society for Parasitology

Language

en

File Format

application/pdf

Available for download on Monday, December 30, 2019

Published Version

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