Regulation of the putative TRPV1t salt taste receptor by phosphatidylinositol 4,5-bisphosphate.
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.
Lyall
Vijay
V
Dept. of Physiology and Biophysics, Virginia Commonwealth Univ., Molecular Medical Research Bldg. 5052, 1220 East Broad St., Richmond, VA 23298, USA. vlyall@vcu.edu
Phan
Tam-Hao T
TH
Ren
ZuoJun
Z
Mummalaneni
Shobha
S
Melone
Pamela
P
Mahavadi
Sunila
S
Murthy
Karnam S
KS
DeSimone
John A
JA
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*
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