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 (PIP2) was studied by monitoring chorda tympani (CT) taste nerve responses to 0.1 M NaCl solutions containing Bz (5 × 10−6 M; a specific ENaC blocker) and resiniferatoxin (RTX; 0–10 × 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 × 10−6 and 1 × 10−6 M. At concentrations >1 × 10−6 M, RTX inhibited the CT response. An increase in PIP2 by topical lingual application of U73122 (a phospholipase C blocker) or diC8-PIP2 (a short chain synthetic PIP2) inhibited the control NaCl + Bz CT response and decreased its sensitivity to RTX. A decrease in PIP2 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 × 10−6 M. The ENaC-dependent NaCl CT responses were not altered by changes in PIP2. An increase in PIP2 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 × 10−6 M) or in TRPV1 KO mice. We conclude that PIP2 is a common intracellular effector for sweet, bitter, umami, and TRPV1t-dependent salt taste, although in the last case, PIP2 seems to directly regulate the taste receptor protein itself, i.e., the TRPV1 ion channel or its taste receptor variant, TRPV1t.

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Effects of osmolarity on taste receptor cell size and function

AJP Cell Physiology ◽

10.1152/ajpcell.1999.277.4.c800 ◽

1999 ◽

Vol 277 (4) ◽

pp. C800-C813 ◽

Cited By ~ 33

Author(s):

Vijay Lyall ◽

Gerard L. Heck ◽

John A. DeSimone ◽

George M. Feldman

Keyword(s):

Cell Volume ◽

Receptor Cell ◽

Taste Receptor ◽

Chorda Tympani ◽

Taste Receptor Cell ◽

Salt Taste ◽

Receptor Cells ◽

Enhanced Ct ◽

And Function ◽

Osmotic Effects

Osmotic effects on salt taste were studied by recording from the rat chorda tympani (CT) nerve and by measuring changes in cell volume of isolated rat fungiform taste receptor cells (TRCs). Mannitol, cellobiose, urea, or DMSO did not induce CT responses. However, the steady-state CT responses to 150 mM NaCl were significantly increased when the stimulus solutions also contained 300 mM mannitol or cellobiose, but not 600 mM urea or DMSO. The enhanced CT responses to NaCl were reversed when the saccharides were removed and were completely blocked by addition of 100 μM amiloride to the stimulus solution. Exposure of TRCs to hyperosmotic solutions of mannitol or cellobiose induced a rapid and sustained decrease in cell volume that was completely reversible, whereas exposure to hypertonic urea or DMSO did not induce sustained reductions in cell volume. These data suggest that the osmolyte-induced increase in the CT response to NaCl involves a sustained decrease in TRC volume and the activation of amiloride-sensitive apical Na+ channels.

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Ethanol Modulates the VR-1 Variant Amiloride-insensitive Salt Taste Receptor. II. Effect on Chorda Tympani Salt Responses

The Journal of General Physiology ◽

10.1085/jgp.200509264 ◽

2005 ◽

Vol 125 (6) ◽

pp. 587-600 ◽

Cited By ~ 27

Author(s):

Vijay Lyall ◽

Gerard L. Heck ◽

Tam-Hao T. Phan ◽

Shobha Mummalaneni ◽

Shahbaz A. Malik ◽

...

Keyword(s):

Elevated Temperature ◽

Direct Action ◽

Taste Receptor ◽

Na Channel ◽

Chorda Tympani ◽

Sprague Dawley ◽

Mineral Salts ◽

Tonic Component ◽

Salt Taste ◽

Nerve Recordings

The effect of ethanol on the amiloride- and benzamil (Bz)-insensitive salt taste receptor was investigated by direct measurement of intracellular Na+ activity ([Na+]i) using fluorescence imaging in polarized fungiform taste receptor cells (TRCs) and by chorda tympani (CT) taste nerve recordings. CT responses to KCl and NaCl were recorded in Sprague-Dawley rats, and in wild-type (WT) and vanilloid receptor-1 (VR-1) knockout mice (KO). CT responses were monitored in the presence of Bz, a specific blocker of the epithelial Na+ channel (ENaC). CT responses were also recorded in the presence of agonists (resiniferatoxin and elevated temperature) and antagonists (capsazepine and SB-366791) of VR-1 that similarly modulate the Bz-insensitive VR-1 variant salt taste receptor. In the absence of mineral salts, ethanol induced a transient decrease in TRC volume and elicited only transient phasic CT responses. In the presence of mineral salts, ethanol increased the apical cation flux in TRCs without a change in volume, increased transepithelial electrical resistance across the tongue, and elicited CT responses that were similar to salt responses, consisting of both a phasic component and a sustained tonic component. At concentrations <50%, ethanol enhanced responses to KCl and NaCl, while at ethanol concentrations >50%, those CT responses were inhibited. Resiniferatoxin and elevated temperature increased the sensitivity of the CT response to ethanol in salt-containing media, and SB-366791 inhibited the effect of ethanol, resiniferatoxin, and elevated temperature on the CT responses to mineral salts. VR-1 KO mice demonstrated no Bz-insensitive CT response to NaCl and no sensitivity to ethanol. We conclude that ethanol increases salt taste sensitivity by its direct action on the Bz-insensitive VR-1 variant salt taste receptor.

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N-geranyl cyclopropyl-carboximide modulates salty and umami taste in humans and animal models

Journal of Neurophysiology ◽

10.1152/jn.00124.2012 ◽

2013 ◽

Vol 109 (4) ◽

pp. 1078-1090 ◽

Cited By ~ 11

Author(s):

Mark L. Dewis ◽

Tam-Hao T. Phan ◽

ZuoJun Ren ◽

Xuanyu Meng ◽

Meng Cui ◽

...

Keyword(s):

Channel Blocker ◽

Monosodium Glutamate ◽

Taste Receptor ◽

Taste Intensity ◽

Chorda Tympani ◽

Wild Type ◽

Salt Taste ◽

Umami Taste ◽

Chicken Broth ◽

Related Compounds

Effects of N-geranyl cyclopropylcarboxamide (NGCC) and four structurally related compounds ( N-cyclopropyl E2,Z6-nonadienamide, N-geranyl isobutanamide, N-geranyl 2-methylbutanamide, and allyl N-geranyl carbamate) were evaluated on the chorda tympani (CT) nerve response to NaCl and monosodium glutamate (MSG) in rats and wild-type (WT) and TRPV1 knockout (KO) mice and on human salty and umami taste intensity. NGCC enhanced the rat CT response to 100 mM NaCl + 5 μM benzamil (Bz; an epithelial Na+ channel blocker) between 1 and 2.5 μM and inhibited it above 5 μM. N-(3-methoxyphenyl)-4-chlorocinnamid (SB-366791, a TRPV1t blocker) inhibited the NaCl+Bz CT response in the absence and presence of NGCC. Unlike the WT mice, no NaCl+Bz CT response was observed in TRPV1 KO mice in the absence or presence of NGCC. NGCC enhanced human salt taste intensity of fish soup stock containing 60 mM NaCl at 5 and 10 μM and decreased it at 25 μM. Rat CT responses to NaCl+Bz and human salt sensory perception were not affected by the above four structurally related compounds. Above 10 μM, NGCC increased the CT response to MSG+Bz+SB-366791 and maximally enhanced the response between 40 and 60 μM. Increasing taste cell Ca2+ inhibited the NGCC-induced increase but not the inosine monophosphate-induced increase in glutamate response. Addition of 45 μM NGCC to chicken broth containing 60 mM sodium enhanced the human umami taste intensity. Thus, depending upon its concentration, NGCC modulates salt taste by interacting with the putative TRPV1t-dependent salt taste receptor and umami taste by interacting with a Ca2+-dependent transduction pathway.

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Malignant lymphoma with middle ear involvement in a Sprague-Dawley rat

Laboratory Animals ◽

10.1177/0023677218764768 ◽

2018 ◽

Vol 52 (4) ◽

pp. 418-423

Author(s):

Jean-Francois Lafond ◽

Annick Landry

Keyword(s):

Malignant Lymphoma ◽

Temporal Bone ◽

Middle Ear ◽

Chorda Tympani ◽

Sprague Dawley ◽

Sprague Dawley Rat ◽

Sprague Dawley Rats ◽

Microscopic Evaluation ◽

Neoplastic Lymphocytes ◽

Tensor Tympani Muscle

Sprague-Dawley rats are amongst the most widely used animals in biomedical research and malignant lymphoma has long been known to be a frequent neoplasm in these animals. A 9-month-old male control Sprague-Dawley rat from a toxicity study showed gelatinous material in the cranial cavity and dark, thickened cerebral meninges at necropsy. At microscopic evaluation of the temporal bone, neoplastic lymphocytes were seen invading several structures of the middle ear. The neoplastic cells appeared to extend from the marrow of the temporal bone, covered the dorsal part of the tympanic cavity wall, and surrounded and infiltrated the base of the tensor tympani muscle as well as the chorda tympani branch of the facial nerve. The lymphoma was generalized; neoplastic lymphocytes were also noted in numerous other tissues. Literature regarding neoplasms of the middle and inner ear in animals is scarce and, to our knowledge, this is the first report of a lymphoma involving the middle ear of a rat.

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Thick ascending limb claudins are altered to increase calciuria and magnesiuria in metabolic acidosis

AJP Renal Physiology ◽

10.1152/ajprenal.00282.2020 ◽

2021 ◽

Author(s):

Il Hwan Oh ◽

Chor Ho Jo ◽

Sua Kim ◽

Sungsin Jo ◽

Sungjin Chung ◽

...

Keyword(s):

Metabolic Acidosis ◽

Immunofluorescence Microscopy ◽

Urinary Calcium ◽

Receptor Protein ◽

Thick Ascending Limb ◽

Sprague Dawley ◽

Calcium Sensing Receptor ◽

Calcium Sensing ◽

Sprague Dawley Rats ◽

Calcium And Magnesium

Urinary calcium and magnesium wasting is a characteristic feature of metabolic acidosis, and this study focused on the role of the thick ascending limb of Henle's loop in metabolic acidosis-induced hypercalciuria and hypermagnesiuria because thick ascending limb is an important site of paracellular calcium and magnesium reabsorption. Male Sprague-Dawley rats were used to determine the effects of acid loading (by adding NH4Cl 7.2 mmol/220 g BW/d to food slurry for 7 days) on renal expression of claudins and then to evaluate whether the results were reversed by antagonizing calcium-sensing receptor (using NPS-2143). At the end of each animal experiment, the kidneys were harvested for immunoblotting, immunofluorescence microscopy and qPCR analysis of claudins and the calcium-sensing receptor. As expected, NH4Cl loading lowered urinary pH and increased excretion of urinary calcium and magnesium. In NH4Cl-loaded rats, renal protein and mRNA expression of claudin-16, and claudin-19 decreased compared with controls. However, claudin-14 protein and mRNA increased in NH4Cl-loaded rats. Consistently, the calcium-sensing receptor protein and mRNA were upregulated in NH4Cl-loaded rats. All these changes were reversed by NPS-2143 coadministration and were confirmed using immunofluorescence microscopy. Hypercalciuria and hypermagnesiuria in NH4Cl-loaded rats were significantly ameliorated by NPS-2143 coadministration as well. We conclude that in metabolic acidosis, claudin-16 and claudin-19 in the thick ascending limb are downregulated to produce hypercalciuria and hypermagnesiuria via the calcium-sensing receptor.

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Role for epithelial Na+channels and putative Na+/H+ exchangers in salt taste transduction in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.6.r1923 ◽

1997 ◽

Vol 273 (6) ◽

pp. R1923-R1931 ◽

Cited By ~ 4

Author(s):

Robert F. Lundy ◽

David W. Pittman ◽

Robert J. Contreras

Keyword(s):

Salt Concentration ◽

Taste Receptor ◽

Drug Dose ◽

Chorda Tympani Nerve ◽

Sprague Dawley ◽

Salt Taste ◽

Receptor Cells ◽

Taste Transduction ◽

Taste Receptor Cells ◽

Dimethyl Amiloride

The effects of the epithelial Na+channel antagonists amiloride and benzamil and the Na+/H+exchange antagonist 5-( N, N-dimethyl)-amiloride (DMA)-Cl on the integrated responses of the chorda tympani nerve to 30, 75, 150, 300, and 500 mM concentrations of NaCl, KCl, and NH4Cl were assessed in male Sprague-Dawley rats. Based on evidence from other systems, 1 and 25 μM amiloride and benzamil were chosen to selectively inhibit epithelial Na+ channels and 1 μM DMA was chosen to selectively inhibit Na+/H+exchange. When added to stimulating salt solutions, amiloride, benzamil, and DMA were each effective in inhibiting responses to all three salts. The degree of inhibition varied with drug, salt, and salt concentration, but not drug dose. Amiloride suppressed NaCl responses to a greater degree than KCl and NH4Cl responses, whereas DMA suppressed NH4Cl responses to a greater degree than NaCl and KCl responses. In all but one case (25 μM amiloride added to KCl), drug suppression of taste nerve responses decreased with an increase in salt concentration. The present results suggest that 1) epithelial Na+ channels in rat taste receptor cells may play a role in KCl and NH4Cl taste transduction; 2) a Na+/H+exchange protein may be present in taste receptor cells, representing a putative component, in addition to epithelial Na+ channels, in salt taste transduction; and 3) salt taste detection and transduction may depend on the utilization of a combination of common and distinct transcellular pathways.

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Differential temperature dependence of taste nerve responses to various taste stimuli in dogs and rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1991.261.6.r1402 ◽

1991 ◽

Vol 261 (6) ◽

pp. R1402-R1408 ◽

Cited By ~ 6

Author(s):

M. Nakamura ◽

K. Kurihara

Keyword(s):

Acetic Acid ◽

Temperature Dependence ◽

Temperature Change ◽

Dose Response ◽

Monosodium Glutamate ◽

Taste Receptor ◽

Chorda Tympani ◽

Chorda Tympani Nerve ◽

Response Curves ◽

Tonic Response

The temperature dependence of the canine and rat chorda tympani nerve responses to various taste stimuli was examined. The temperature dependence greatly varied with species of stimuli. In the dog, the tonic responses to fructose, sucrose, acetic acid, and guanosine 5'-monophosphate (GMP) and the response induced by the synergism between monosodium glutamate (MSG) and GMP showed peaks at approximately 30 degrees C, whereas those to NaCl, NH4Cl, and MSG showed peaks between 10 and 20 degrees C. In the rat, the tonic response to NH4Cl increased with an increase in temperature up to 45 degrees C, whereas the responses to other stimuli examined showed peaks at approximately 30 degrees C. The responses to glycine, sucrose, and quinine showed sharp temperature dependence, and the responses to acids (HCl and acetic acid) and salts (NaCl and KCl) showed relatively flat dependence. The effects of the temperature change on dose-response curves for fructose, NH4Cl, and GMP were examined using dogs. The temperature change did not practically affect the thresholds for these stimuli and affected the magnitude of the responses to higher concentrations of stimuli. The origins of the temperature dependence were discussed in terms of taste receptor mechanisms.

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