A Novel Vanilloid Receptor-1 (VR-1) Variant Mammalian Salt Taste Receptor

Lyall, Vijay; Heck, Gerard L.; Vinnikova, Anna K.; Ghosh, Shobha; Phan, Tam-Hao T.; DeSimone, John A.

doi:10.1093/chemse/bjh104

Cited by 41 publications

(133 citation statements)

References 3 publications

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“…The rinse solution (R) was 10 mM KCl, and stimulating solutions contained 100 mM NaCl; 100 mM NaCl ϩ 5 M Bz, a specific blocker of ENaC; 100 mM NaCl ϩ 5 M Bz ϩ 1 M SB-366791 (SB), a specific blocker of TRPV1; 100 mM NaCl ϩ 5 M Bz ϩ RTX (0 -10 M), a specific agonist of TRPV1 (26,27); and 100 mM NaCl ϩ 5 M Bz ϩ RTX (0 -10 M) ϩ 10 M CZP, a blocker of TRPV1. Bz, SB, CZP, and RTX were obtained from Sigma-Aldrich.…”

Section: Methodsmentioning

confidence: 99%

“…We monitored the CT response to 100 mM NaCl ϩ 5 M Bz in Sprague-Dawley rats, WT mice, TRPV1 KO mice, TRPM5 KO mice, and PLC␤ 2 KO mice in the absence and presence of varying concentrations of the TRPV1 agonist resiniferatoxin (RTX). In rats, CT responses were also monitored after topical lingual application of triphenylphosphine oxide (TPPO), a specific blocker of the TRPM5 cation channel (38), and in the presence of capsazepine (CZP) and SB-366791, specific blockers of TRPV1 and the Bz-insensitive NaCl CT response (15,26,27). Our results show that the CT response at 100 mM NaCl was significantly smaller in TRPM5 KO than WT mice.…”

mentioning

confidence: 90%

“…The TRPV1t channel is insensitive to amiloride and Bz, permeable to Na ϩ , K ϩ , NH 4 ϩ , and Ca 2ϩ , and contributes to cell depolarization (31). These conclusions are supported by the observations that the phasic (transient) and tonic (steady-state) components of the chorda tympani (CT) taste nerve response to NaCl are inhibited to the baseline rinse level in TRPV1 knockout (KO) mice stimulated with NaCl ϩ Bz and in wild-type (WT) mice and rats in the presence of NaCl ϩ Bz ϩ N-(3-methoxyphenyl)-4-chlorocinnamid (SB-366791, a TRPV1 blocker) (26,27). Several agonists and antagonists of TRPV1 modulate the Bz-insensitive NaCl CT responses in animal models and alter human salt taste (11, 20, 26 -30, 40, 41, 48).…”

mentioning

confidence: 98%

“…One channel type is the Na ϩ -specific epithelial Na ϩ channel (ENaC), in which Na ϩ transport is inhibited by amiloride and benzamil (Bz) (1,3,8). The second involves Na ϩ transport through a putative transient receptor potential (TRP) vanilloid subfamily member 1 (TRPV1t)-nonspecific cation channel (26,27). The TRPV1t channel is insensitive to amiloride and Bz, permeable to Na ϩ , K ϩ , NH 4 ϩ , and Ca 2ϩ , and contributes to cell depolarization (31).…”

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confidence: 99%

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TRPM5-dependent amiloride- and benzamil-insensitive NaCl chorda tympani taste nerve response

Ren

Rhyu

Phan

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Ren Z, Rhyu M, Phan TT, Mummalaneni S, Murthy KS, Grider JR, DeSimone JA, Lyall V. TRPM5-dependent amilorideand benzamil-insensitive NaCl chorda tympani taste nerve response. Am J Physiol Gastrointest Liver Physiol 305: G106 -G117, 2013. First published May 2, 2013; doi:10.1152/ajpgi.00053.2013.-Transient receptor potential (TRP) subfamily M member 5 (TRPM5) cation channel is involved in sensing sweet, bitter, umami, and fat taste stimuli, complex-tasting divalent salts, and temperature-induced changes in sweet taste. To investigate if the amiloride-and benzamil (Bz)-insensitive NaCl chorda tympani (CT) taste nerve response is also regulated in part by TRPM5, CT responses to 100 mM NaCl ϩ 5 M Bz (NaCl ϩ Bz) were monitored in Sprague-Dawley rats, wild-type (WT) mice, and TRP vanilloid subfamily member 1 (TRPV1) and TRPM5 knockout (KO) mice in the presence of resiniferatoxin (RTX), a TRPV1 agonist. In rats, NaCl ϩ Bz ϩ RTX CT responses were also monitored in the presence of triphenylphosphine oxide, a specific TRPM5 blocker, and capsazepine and N-(3-methoxyphenyl)-4-chlorocinnamid (SB-366791), specific TRPV1 blockers. In rats and WT mice, RTX produced biphasic effects on the NaCl ϩ Bz CT response, enhancing the response at 0.5-1 M and inhibiting it at Ͼ1 M. The NaCl ϩ Bz ϩ SB-366791 CT response in rats and WT mice and the NaCl ϩ Bz CT response in TRPV1 KO mice were inhibited to baseline level and were RTX-insensitive. In rats, blocking TRPV1 by capsazepine or TRPM5 by triphenylphosphine oxide inhibited the tonic NaCl ϩ Bz CT response and shifted the relationship between RTX concentration and the magnitude of the tonic CT response to higher RTX concentrations. TRPM5 KO mice elicited no constitutive NaCl ϩ Bz tonic CT response. The relationship between RTX concentration and the magnitude of the tonic NaCl ϩ Bz CT response was significantly attenuated and shifted to higher RTX concentrations. The results suggest that pharmacological or genetic alteration of TRPM5 activity modulates the Bz-insensitive NaCl CT response and its modulation by TRPV1 agonists. triphenylphosphine oxide; resiniferatoxin; capsazepine; SB-366791; TRPV1 APPETITIVE AND AVERSIVE NEURAL and behavioral responses to NaCl are most likely transduced by a variety of mechanisms (35). Several studies suggest that in the anterior tongue Na ϩ from a Na ϩ salt taste stimulus enters a subset of taste bud cells by at least two types of cation channels located in taste cell apical membranes. One channel type is the Na ϩ -specific epithelial Na ϩ channel (ENaC), in which Na ϩ transport is inhibited by amiloride and benzamil (Bz) (1, 3, 8). The second involves Na ϩ transport through a putative transient receptor potential (TRP) vanilloid subfamily member 1 (TRPV1t)-nonspecific cation channel (26,27). The TRPV1t channel is insensitive to amiloride and Bz, permeable to Na ϩ , K ϩ , NH 4 ϩ , and Ca 2ϩ , and contributes to cell depolarization (31). These conclusions are supported by the observations that the phasic (transient) and tonic (steady-state) components of ...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 90%

mentioning

confidence: 98%

mentioning

confidence: 99%

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TRPM5-dependent amiloride- and benzamil-insensitive NaCl chorda tympani taste nerve response

Ren

Rhyu

Phan

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The TRPV1 contribution to the behavioral data is likely to come from its expression in somatosensory nociceptors and/or from its expression in TRPM5 cells that contain TRPV1t and that evoke an aversive response (Lyall et al, 2004(Lyall et al, , 2005Hacker and Medler, 2008).…”

Section: The Taste Of Ctds Has Multiple Components and Depends On Conmentioning

confidence: 99%

Sensory Attributes of Complex Tasting Divalent Salts Are Mediated by TRPM5 and TRPV1 Channels

Riera¹,

Vogel²,

Simon³

et al. 2009

J. Neurosci.

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Complex tasting divalent salts (CTDS) are present in our daily diet, contributing to multiple poorly understood taste sensations. CTDS evoking metallic, bitter, salty, and astringent sensations include the divalent salts of iron, zinc, copper, and magnesium. To identify pathways involved with the complex perception of the above salts, taste preference tests (two bottles, brief access) were performed in wild-type (WT) mice and in mice lacking (1) the T1R3 receptor, (2) TRPV1, the capsaicin receptor, or (3) the TRPM5 channel, the latter being necessary for the perception of sweet, bitter, and umami tasting stimuli. At low concentrations, FeSO 4 and ZnSO 4 were perceived as pleasant stimuli by WT mice, and this effect was fully reversed in TRPM5 knock-out mice. In contrast, MgSO 4 and CuSO 4 were aversive to WT mice, but for MgSO 4 the aversion was abolished in TRPM5 knock-out animals, and for CuSO 4 , aversion decreased in both TRPV1-and TRPM5-deficient animals. Behavioral tests revealed that the T1R3 subunit of the sweet and umami receptors is implicated in the hedonically positive perception of FeSO 4 and ZnSO 4 . For high concentrations of CTDS, the omission of TRPV1 reduced aversion. Imaging studies on heterologously expressed TRPM5 and TRPV1 channels are consistent with the behavioral experiments. Together, these results rationalize the complexity of metallic taste by showing that at low concentrations, compounds such as FeSO 4 and ZnSO 4 stimulate the gustatory system through the hedonically positive T1R3-TRPM5 pathway, and at higher concentrations, their aversion is mediated, in part, by the activation of TRPV1.

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Spices: The Savory and Beneficial Science of Pungency

Nilius

Appendino

2013

Reviews of Physiology, Biochemistry and Pharmacology

133

118

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Spicy food does not only provide an important hedonic input in daily life, but has also been anedoctically associated to beneficial effects on our health. In this context, the discovery of chemesthetic trigeminal receptors and their spicy ligands has provided the mechanistic basis and the pharmacological means to investigate this enticing possibility. This review discusses in molecular terms the connection between the neurophysiology of pungent spices and the "systemic" effects associated to their trigeminality. It commences with a cultural and historical overview on the Western fascination for spices, and, after analysing in detail the mechanisms underlying the trigeminality of food, the main dietary players from the transient receptor potential (TRP) family of cation channels are introduced, also discussing the "alien" distribution of taste receptors outside the oro-pharingeal cavity. The modulation of TRPV1 and TRPA1 by spices is next described, discussing how spicy sensations can be turned into hedonic pungency, and analyzing the mechanistic bases for the health benefits that have been associated to the consumption of spices. These include, in addition to a beneficial modulation of gastro-intestinal and cardio-vascular function, slimming, the optimization of skeletal muscle performance, the reduction of chronic inflammation, and the prevention of metabolic syndrome and diabetes. We conclude by reviewing the role of electrophilic spice constituents on cancer prevention in the light of their action on pro-inflammatory and pro-cancerogenic nuclear factors like NFκB, and on their interaction with the electrophile sensor protein Keap1 and the ensuing Nrf2-mediated transcriptional activity. Spicy compounds have a complex polypharmacology, and just like any other bioactive agent, show a balance of beneficial and bad actions. However, at least for moderate consumption, the balance seems definitely in favour of the positive side, suggesting that a spicy diet, a caveman-era technology, could be seriously considered in addition to caloric control and exercise as a measurement to prevent and control many chronic diseases associate to malnutrition from a Western diet.

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A Novel Vanilloid Receptor-1 (VR-1) Variant Mammalian Salt Taste Receptor

Cited by 41 publications

References 3 publications

TRPM5-dependent amiloride- and benzamil-insensitive NaCl chorda tympani taste nerve response

TRPM5-dependent amiloride- and benzamil-insensitive NaCl chorda tympani taste nerve response

Sensory Attributes of Complex Tasting Divalent Salts Are Mediated by TRPM5 and TRPV1 Channels

Spices: The Savory and Beneficial Science of Pungency

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