title: 3-phosphoinositides modulate cyclic nucleotide signaling in olfactory receptor neurons.
abstract: Phosphatidylinositol 3-kinase (PI3K)-dependent phosphoinositide signaling has been implicated in diverse cellular systems coupled to receptors for many different ligands, but the extent to which it functions in sensory transduction is yet to be determined. We now report that blocking PI3K activity increases odorant-evoked, cyclic nucleotide-dependent elevation of [Ca(2+)](i) in acutely dissociated rat olfactory receptor neurons and does so in an odorant-specific manner. These findings imply that 3-phosphoinositide signaling acts in vertebrate olfactory transduction to inhibit cyclic nucleotide-dependent excitation of the cells and that the interaction of the two signaling pathways is important in odorant coding, indicating that 3-phosphoinositide signaling can play a role in sensory transduction.
authors.affiliation: Department of Cell Physiology, Ruhr University Bochum, Bochum, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Spehr
authors.forename: Christian H
authors.initials: CH
authors.lastname: Wetzel
authors.forename: Hanns
authors.initials: H
authors.lastname: Hatt
authors.forename: Barry W
authors.initials: BW
authors.lastname: Ache
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004594:Electrophysiology / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D009812:Odorants; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012903:Smell / Q000502:physiology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002118:Calcium; D002867:Chromones; D004791:Enzyme Inhibitors; D004963:Estrenes; D009025:Morpholines; D009712:Nucleotides, Cyclic; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011760:Pyrrolidinones; D010738:Type C Phospholipases; D000077191:Wortmannin; C060974:phosphatidylinositol 3,4,5-triphosphate; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one