Insect repellents: modulators of mosquito odorant receptor activity.
BACKGROUND
DEET, 2-undecanone (2-U), IR3535 and Picaridin are widely used as insect repellents to prevent interactions between humans and many arthropods including mosquitoes. Their molecular action has only recently been studied, yielding seemingly contradictory theories including odorant-dependent inhibitory and odorant-independent excitatory activities on insect olfactory sensory neurons (OSNs) and odorant receptor proteins (ORs).


RESULTS
Here we characterize the action of these repellents on two Aedes aegypti ORs, AaOR2 and AaOR8, individually co-expressed with the common co-receptor AaOR7 in Xenopus oocytes; these ORs are respectively activated by the odors indole (AaOR2) and (R)-(-)-1-octen3-ol (AaOR8), odorants used to locate oviposition sites and host animals. In the absence of odorants, DEET activates AaOR2 but not AaOR8, while 2-U activates AaOR8 but not AaOR2; IR3535 and Picaridin do not activate these ORs. In the presence of odors, DEET strongly inhibits AaOR8 but not AaOR2, while 2-U strongly inhibits AaOR2 but not AaOR8; IR3535 and Picaridin strongly inhibit both ORs.


CONCLUSIONS
These data demonstrate that repellents can act as olfactory agonists or antagonists, thus modulating OR activity, bringing concordance to conflicting models.
Bohbot
Jonathan D
JD
Invasive Insect Biocontrol and Behavior Laboratory, Henry A. Wallace Beltsville Agricultural Research Center, Plant Sciences Institute, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland, United States of America.
Dickens
Joseph C
JC
D000330:Aedes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D007302:Insect Repellents / Q000494:pharmacology*; D000442:Octanols / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000378:metabolism; D018035:Receptors, Odorant / Q000819:agonists / Q000378:metabolism*
D007211:Indoles; D007302:Insect Repellents; D000442:Octanols; D018035:Receptors, Odorant; C038844:1-octen-3-ol