title: PI3Kgamma-dependent signaling in mouse olfactory receptor neurons.
abstract: 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.
authors.affiliation: Center for Smell and Taste, University of Florida, Gainesville, FL 32610-0127 USA. daniela.brunert@rub.de
authors.forename: Daniela
authors.initials: D
authors.lastname: Brunert
authors.forename: Katharina
authors.initials: K
authors.lastname: Klasen
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Corey
authors.forename: Barry W
authors.initials: BW
authors.lastname: Ache
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D058544:Class Ib Phosphatidylinositol 3-Kinase; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009812:Odorants; D018034:Olfactory Receptor Neurons / Q000201:enzymology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002118:Calcium; D058544:Class Ib Phosphatidylinositol 3-Kinase; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms; C546765:Pik3cg protein, rat; C546764:Pik3cg protein, mouse