Odorant receptor modulation: Ternary paradigm for mode of action of insect repellents

Jonathan D. Bohbot; Joseph C. Dickens

doi:10.1016/j.neuropharm.2012.01.004

Odorant receptor modulation: Ternary paradigm for mode of action of insect repellents

Research output: Contribution to journal › Article › peer-review

Abstract

The modulation of insect behavior for the purpose of controlling the spread of infectious diseases has been the task of a few insect repellents for which the mechanistic modes of action on odorant receptors (ORs) are unclear. Here, we study the effects of the repellents DEET and IR3535, and a novel OR co-receptor (Orco) agonist on odorant-evoked currents in Xenopus oocytes expressing two subtypes of Aedes aegypti ORs (AaORs). We show that DEET and IR3535 behave as insurmountable antagonists of ORs, and that modulation of OR activity is not restricted to antagonism and agonism, but also includes synergism. This knowledge of the molecular mechanisms underlying OR blockade, activation and hyperactivation will be fundamental to the development of novel strategies for the control of mosquito behavior.

Original language	English
Pages (from-to)	2086-2095
Number of pages	10
Journal	Neuropharmacology
Volume	62
Issue number	5-6
DOIs	https://doi.org/10.1016/j.neuropharm.2012.01.004
State	Published - Apr 2012
Externally published	Yes

Keywords

Aedes aegypti
Agonist
Insect repellent
Insurmountable antagonist
Mosquito
Odorant receptor
Olfaction
OrcoRAM
VUAA1

All Science Journal Classification (ASJC) codes

Pharmacology
Cellular and Molecular Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.neuropharm.2012.01.004

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title = "Odorant receptor modulation: Ternary paradigm for mode of action of insect repellents",

abstract = "The modulation of insect behavior for the purpose of controlling the spread of infectious diseases has been the task of a few insect repellents for which the mechanistic modes of action on odorant receptors (ORs) are unclear. Here, we study the effects of the repellents DEET and IR3535, and a novel OR co-receptor (Orco) agonist on odorant-evoked currents in Xenopus oocytes expressing two subtypes of Aedes aegypti ORs (AaORs). We show that DEET and IR3535 behave as insurmountable antagonists of ORs, and that modulation of OR activity is not restricted to antagonism and agonism, but also includes synergism. This knowledge of the molecular mechanisms underlying OR blockade, activation and hyperactivation will be fundamental to the development of novel strategies for the control of mosquito behavior.",

keywords = "Aedes aegypti, Agonist, Insect repellent, Insurmountable antagonist, Mosquito, Odorant receptor, Olfaction, OrcoRAM, VUAA1",

author = "Bohbot, {Jonathan D.} and Dickens, {Joseph C.}",

note = "Funding Information: The authors are grateful to Drs. Jason Pitts (Vanderbilt University), Thomas Heinbockel and Ze-Jun Wang (Howard University) for their critical reading of the manuscript. We also thank Dr. Laurence Zwiebel for providing the AaOr10 expression vector and a small amount of VUAA1. We offer special thanks to Drs. Liezhen Fu and Yun-Bo Shi (National Institutes of Health) for graciously providing Xenopus oocytes. This work was supported in part by a grant to J.C.D. from the Deployed War Fighter Protection (DWFP) Research Program, funded by the US Department of Defense through the Armed Forces Pest Management Board (AFPMB).",

year = "2012",

month = apr,

doi = "10.1016/j.neuropharm.2012.01.004",

language = "الإنجليزيّة",

volume = "62",

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journal = "Neuropharmacology",

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KW - Olfaction

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M3 - مقالة

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SP - 2086

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JO - Neuropharmacology

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ER -

Odorant receptor modulation: Ternary paradigm for mode of action of insect repellents

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

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