title: Regulation of the putative TRPV1t salt taste receptor by phosphatidylinositol 4,5-bisphosphate.
abstract: Regulation of the putative amiloride and benzamil (Bz)-insensitive TRPV1t salt taste receptor by phosphatidylinositol 4,5-bisphosphate (PIP(2)) was studied by monitoring chorda tympani (CT) taste nerve responses to 0.1 M NaCl solutions containing Bz (5 x 10(-6) M; a specific ENaC blocker) and resiniferatoxin (RTX; 0-10 x 10(-6) M; a specific TRPV1 agonist) in Sprague-Dawley rats and in wildtype (WT) and TRPV1 knockout (KO) mice. In rats and WT mice, RTX elicited a biphasic effect on the NaCl + Bz CT response, increasing the CT response between 0.25 x 10(-6) and 1 x 10(-6) M. At concentrations >1 x 10(-6) M, RTX inhibited the CT response. An increase in PIP(2) by topical lingual application of U73122 (a phospholipase C blocker) or diC8-PIP(2) (a short chain synthetic PIP(2)) inhibited the control NaCl + Bz CT response and decreased its sensitivity to RTX. A decrease in PIP(2) by topical lingual application of phenylarsine oxide (a phosphoinositide 4 kinase blocker) enhanced the control NaCl + Bz CT response, increased its sensitivity to RTX stimulation, and inhibited the desensitization of the CT response at RTX concentrations >1 x 10(-6) M. The ENaC-dependent NaCl CT responses were not altered by changes in PIP(2). An increase in PIP(2) enhanced CT responses to sweet (0.3 M sucrose) and bitter (0.01 M quinine) stimuli. RTX produced the same increase in the Bz-insensitive Na(+) response when present in salt solutions containing 0.1 M NaCl + Bz, 0.1 M monosodium glutamate + Bz, 0.1 M NaCl + Bz + 0.005 M SC45647, or 0.1 M NaCl + Bz + 0.01 M quinine. No effect of RTX was observed on CT responses in WT mice and rats in the presence of the TRPV1 blocker N-(3-methoxyphenyl)-4-chlorocinnamide (1 x 10(-6) M) or in TRPV1 KO mice. We conclude that PIP(2) is a common intracellular effector for sweet, bitter, umami, and TRPV1t-dependent salt taste, although in the last case, PIP(2) seems to directly regulate the taste receptor protein itself, i.e., the TRPV1 ion channel or its taste receptor variant, TRPV1t.
authors.affiliation: Dept. of Physiology and Biophysics, Virginia Commonwealth Univ., Molecular Medical Research Bldg. 5052, 1220 East Broad St., Richmond, VA 23298, USA. vlyall@vcu.edu
authors.forename: Vijay
authors.initials: V
authors.lastname: Lyall
authors.forename: Tam-Hao T
authors.initials: TH
authors.lastname: Phan
authors.forename: ZuoJun
authors.initials: Z
authors.lastname: Ren
authors.forename: Shobha
authors.initials: S
authors.lastname: Mummalaneni
authors.forename: Pamela
authors.initials: P
authors.lastname: Melone
authors.forename: Sunila
authors.initials: S
authors.lastname: Mahavadi
authors.forename: Karnam S
authors.initials: KS
authors.lastname: Murthy
authors.forename: John A
authors.initials: JA
authors.lastname: DeSimone
mesh_terms: D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D002814:Chorda Tympani Nerve / Q000187:drug effects; D002855:Chromatography, Thin Layer; D017931:DNA Primers; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D053503:Epithelial Sodium Channels / Q000502:physiology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006146:Guanidines; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000494:pharmacology*; D011803:Quinine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology*; D013549:Sweetening Agents / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D013649:Taste / Q000187:drug effects; D013650:Taste Buds / Q000187:drug effects*
chemical_list: D001152:Arsenicals; D017931:DNA Primers; D004224:Diterpenes; D053503:Epithelial Sodium Channels; D006146:Guanidines; D019269:Phosphatidylinositol 4,5-Diphosphate; C099860:SC 45647; D013549:Sweetening Agents; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C493922:Trpv1 protein, rat; C029341:oxophenylarsine; D012965:Sodium Chloride; C024353:resiniferatoxin; D011803:Quinine