PI3Kgamma-dependent signaling in mouse olfactory receptor neurons.

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, PI3Kbeta and PI3Kgamma, 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 PI3Kgamma, 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 PI3Kgamma plays a role in mediating inhibition of odorant responses in mammalian ORNs.