Journal
CHEMICAL SENSES
Volume 35, Issue 4, Pages 301-308Publisher
OXFORD UNIV PRESS
DOI: 10.1093/chemse/bjq020
Keywords
calcium imaging; complex odorants; ELISA; inhibitory input; transgenic
Funding
- National Institute on Deafness and Other Communication Disorders [DC05512, DC009730]
- Deutsche Forschungsgemeinschaft
- Alexander von Humboldt Foundation
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Phosphatidylinositol 3-kinase (PI3K)-dependent signaling couples to receptors for many different ligands in diverse cellular systems. Recent findings suggest that PI3K-dependent signaling also mediates inhibition of odorant responses in rat olfactory receptor neurons (ORNs). Here, we present evidence that murine ORNs show PI3K-dependent calcium responses to odorant stimulation, they express 2 G protein-coupled receptor (GPCR)-activated isoforms of PI3K, PI3K beta and PI3K gamma, and they exhibit odorant-induced PI3K activity. These findings support our use of a transgenic mouse model to begin to investigate the mechanisms underlying PI3K-mediated inhibition of odorant responses in mammalian ORNs. Mice deficient in PI3K gamma, a class IB PI3K that is activated via GPCRs, lack detectable odorant-induced PI3K activity in their olfactory epithelium and their ORNs are less sensitive to PI3K inhibition. We conclude that odorant-dependent PI3K signaling generalizes to the murine olfactory system and that PI3K gamma plays a role in mediating inhibition of odorant responses in mammalian ORNs.
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