title: Resynthesis of phosphatidylinositol 4,5-bisphosphate mediates adaptation of the caffeine response in rat taste receptor cells.
abstract: Caffeine, a prototypic bitter stimulus, produces several physiological actions on taste receptor cells that include inhibition of KIR and KV potassium currents and elevations of intracellular calcium. These responses display adaptation, i.e. their magnitude diminishes in the sustained presence of the stimulus. Levels of the membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP2) are well known to modulate many potassium channels, activating the channel by stabilizing its open state. Here we investigate a putative relationship of KIR and KV with PIP2 levels hypothesizing that inhibition of these currents by caffeine might be allayed by PIP2 resynthesis. Using standard patch-clamp techniques, recordings of either potassium current from rat posterior taste receptor cells produced essentially parallel results when PIP2 levels were manipulated pharmacologically. Increasing PIP2 levels by blocking phosphoinositide-3 kinase with wortmannin or LY294002, or by blocking phospholipase C with U73122 all significantly increased the incidence of adaptation for both KIR and KV. Conversely, lowering PIP2 synthesis by blocking PI4K or using the PIP2 scavengers polylysine or bovine serum albumin reduced the incidence of adaptation. Adaptation could be modulated by activation of protein kinase C but not calcium calmodulin kinase. Collectively, these data support two highly novel conclusions: potassium currents in taste receptor cells are significantly modulated by PIP2 levels and PIP2 resynthesis may play a central role in the gustatory adaptation process at the primary receptor cell level.
authors.affiliation: College of Dentistry, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Fang-Li
authors.initials: FL
authors.lastname: Zhao
authors.forename: Scott
authors.initials: S
authors.lastname: Herness
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors; D002867:Chromones / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054799:Phospholipase C beta / Q000037:antagonists & inhibitors; D011107:Polylysine / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013649:Taste / Q000187:drug effects / Q000502:physiology*; D013650:Taste Buds / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000077191:Wortmannin; D000096926:Benzenesulfonamides
chemical_list: D000730:Androstadienes; D001596:Benzylamines; D002110:Caffeine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002867:Chromones; D051668:Delayed Rectifier Potassium Channels; D004791:Enzyme Inhibitors; D004963:Estrenes; D009025:Morpholines; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D000081082:Phosphoinositide-3 Kinase Inhibitors; D054799:Phospholipase C beta; D011107:Polylysine; D024661:Potassium Channels, Inwardly Rectifying; D011493:Protein Kinase C; D011760:Pyrrolidinones; D012710:Serum Albumin, Bovine; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate; 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; C072105:KN 93; D000096926:Benzenesulfonamides; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C518038:Plcb2 protein, rat