title: Phosphoinositide 3-kinase dependent inhibition as a broad basis for opponent coding in Mammalian olfactory receptor neurons.
abstract: Phosphoinositide 3-kinase (PI3K) signaling has been implicated in mediating inhibitory odorant input to mammalian olfactory receptor neurons (ORNs). To better understand the breadth of such inhibition in odor coding, we screened a panel of odorants representing different chemical classes, as well as odorants known to occur in a natural odor object (tomato), for their ability to rapidly activate PI3K-dependent inhibitory signaling. Odorants were screened on dissociated native rat ORNs before and after pre-incubation with the PI3K-isoform specific blockers AS252424 and TGX221. Many different odorants increased their excitatory strength for particular ORNs following PI3K blockade in a manner consistent with activating PI3K-dependent inhibitory signaling in those cells. The PI3K-dependent inhibitory odorants overlapped with conventional excitatory odorants, but did not share the same bias, indicating partial partitioning of the odor space. Finding that PI3K-dependent inhibition can be activated by a wide range of otherwise conventional excitatory odorants strongly implies PI3K-dependent inhibition provides a broad basis for opponent coding in mammalian ORNs.
authors.affiliation: Whitney Laboratory, Center for Smell and Taste, McKnight Brain Institute; University of Florida, Gainesville, Florida, United States of America. ukhanov@mbi.ufl.edu
authors.forename: Kirill
authors.initials: K
authors.lastname: Ukhanov
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; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009025:Morpholines / Q000494:pharmacology; D009812:Odorants / Q000032:analysis*; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D061251:Primary Cell Culture; D011744:Pyrimidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018035:Receptors, Odorant / Q000378:metabolism*; D015398:Signal Transduction; D054852:Small Molecule Libraries / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D002118:Calcium; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011744:Pyrimidinones; D018035:Receptors, Odorant; D054852:Small Molecule Libraries; D045162:Thiazolidinediones; C512438:5-(5-(4-fluoro-2-hydroxyphenyl)furan-2-ylmethylene)thiazolidine-2,4-dione; C504718:TGX 221