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

Jonathan D. Bohbot, Joseph C. Dickens*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

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 languageAmerican English
Pages (from-to)2086-2095
Number of pages10
JournalNeuropharmacology
Volume62
Issue number5-6
DOIs
StatePublished - Apr 2012
Externally publishedYes

Bibliographical 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).

Keywords

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

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