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

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

doi:10.1085/jgp.200509264

Cited by 33 publications

(70 citation statements)

References 41 publications

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“…1), Sprague-Dawley rats, alcohol-preferring (P) rats, and alcohol-non-preferring (NP) rats (6,26). In addition, several low-affinity blockers that inhibit the Bz-insensitive NaCl CT response in the micromolarto-millimolar range include RTX, capsaicin, cetylpyridinium chloride, Maillard reacted peptides (MRPs), N-geranylcyclopropylcarboximide, ethanol, and nicotine (6,11,20,26,27,29,30,40,41,48). Our whole nerve data are supported by the effect of TRPV1 agonists on single CT nerve fibers.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…A taste variant of TRPV1 has been identified in taste cells (Lyall et al 2004(Lyall et al , 2005Treesukosol et al 2007) but the physiological role of this channel in taste cells has not been characterized. There are also conflicting reports within the field as to whether TRPV1 is expressed in taste cells (Lyall et al 2004(Lyall et al , 2005Treesukosol et al 2007) or if its expression is restricted to the nerve fibers that innervate taste buds (Ishida et al 2002). Our data support the expression of TRPV1 in the taste receptor cells, because all of our experiments were performed on acutely isolated taste receptor cells, including the capsaicininduced calcium responses.…”

Section: Discussionmentioning

confidence: 99%

“…These channels include the calcium-sensitive TRPM5 (Perez et al 2002(Perez et al , 2003Prawitt et al 2003), a taste variant of TRPV1 (Lyall et al 2004(Lyall et al , 2005, and a heteromer of Pkd1l3/Pkd2l1 (Huang et al 2006;Ishimaru et al 2006;LopezJimenez et al 2006). All three of these channels have been implicated in taste transduction, but their physiological roles have not been clearly defined.…”

Section: What Channels Contribute To This Constitutive Calcium Influxmentioning

confidence: 99%

Mitochondrial Calcium Buffering Contributes to the Maintenance of Basal Calcium Levels in Mouse Taste Cells

Hacker¹,

Medler²

2008

Journal of Neurophysiology

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Hacker K, Medler KF. Mitochondrial calcium buffering contributes to the maintenance of basal calcium levels in mouse taste cells. J Neurophysiol 100: 2177-2191. First published August 6, 2008 doi:10.1152/jn.90534.2008. Taste stimuli are detected by taste receptor cells present in the oral cavity using diverse signaling pathways. Some taste stimuli are detected by G protein-coupled receptors (GPCRs) that cause calcium release from intracellular stores, whereas other stimuli depolarize taste cells to cause calcium influx through voltage-gated calcium channels (VGCCs). Although taste cells use two distinct mechanisms to transmit taste signals, increases in cytosolic calcium are critical for normal responses in both pathways. This creates a need to tightly control intracellular calcium levels in all transducing taste cells. To date, however, the mechanisms used by taste cells to regulate cytosolic calcium levels have not been identified. Studies in other cell types have shown that mitochondria can be important calcium buffers, even during small changes in calcium loads. In this study, we used calcium imaging to characterize the role of mitochondria in buffering calcium levels in taste cells. We discovered that mitochondria make important contributions to the maintenance of resting calcium levels in taste cells by routinely buffering a constitutive calcium influx across the plasma membrane. This is unusual because in other cell types, mitochondrial calcium buffering primarily affects large evoked calcium responses. We also found that the amount of calcium that is buffered by mitochondria varies with the signaling pathways used by the taste cells. A transient receptor potential (TRP) channel, likely TRPV1 or a taste variant of TRPV1, contributes to the constitutive calcium influx. I N T R O D U C T I O NThe detection of gustatory stimuli depends on the activation of taste receptor cells located in taste buds within the oral cavity. Activated taste receptors on the apical membrane of taste cells initiate transduction pathways that ultimately transmit signals to afferent gustatory neurons. Taste cells use two distinct signaling pathways to mediate their communication to the nervous system: 1) calcium influx through voltage-gated calcium channels (VGCCs), which causes vesicular neurotransmitter release or 2) G proteincoupled receptor (GPCR)-dependent second messenger pathways that activate a calcium-dependent nonvesicular mechanism to release the neurotransmitter, ATP (Clapp et al. 2004(Clapp et al. , 2006DeFazio et al. 2006;Finger et al. 2005;Huang et al. 2007;Romanov et al. 2007;Tomchik et al. 2007). Both signaling mechanisms depend on increasing cytosolic calcium to produce normal synaptic signals. Hence all transducing taste cells must tightly regulate intracellular calcium levels. Currently, the role of buffering mechanisms to control cytosolic calcium levels in taste cells has not been described.In addition to its role in ATP production, mitochondria make significant contributions to the regulation cytosolic calci...

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“…The curves were generated using a fitting function that models the characteristic biphasic property of the RTX concentration versus the magnitude of the chorda tympani response. The biphasic property has been observed with every agonist of amiloride-and Bz-insensitive NaCl chorda tympani response thus far examined (Katsumata et al 2008;Lyall et al , 2005b. The fitting function used was…”

Section: Chorda Tympani Nerve Recordingsmentioning

confidence: 99%

Regulation of the Benzamil-Insensitive Salt Taste Receptor by Intracellular Ca²⁺, Protein Kinase C, and Calcineurin

Lyall

Phan²,

Mummalaneni³

et al. 2009

Journal of Neurophysiology

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Ϫ6 M) or in TRPV1 KO mice. 32 Plabeling demonstrated direct phosphorylation of TRPV1 or TRPV1t in anterior lingual epithelium by PMA, cyclosporin A, or FK-506. PMA also enhanced the RTX-sensitive unilateral apical Na ϩ flux in polarized fungiform TRC in vitro. We conclude that TRPV1 or its variant TRPV1t is phosphorylated and dephosphorylated by PKC and PP2B, respectively, and either sensitizes or desensitizes the Bz-insensitive NaCl chorda tympani responses to RTX stimulation.

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

Cited by 33 publications

References 41 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

Mitochondrial Calcium Buffering Contributes to the Maintenance of Basal Calcium Levels in Mouse Taste Cells

Regulation of the Benzamil-Insensitive Salt Taste Receptor by Intracellular Ca²⁺, Protein Kinase C, and Calcineurin

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

Cited by 33 publications

References 41 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

Mitochondrial Calcium Buffering Contributes to the Maintenance of Basal Calcium Levels in Mouse Taste Cells

Regulation of the Benzamil-Insensitive Salt Taste Receptor by Intracellular Ca2+, Protein Kinase C, and Calcineurin

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Regulation of the Benzamil-Insensitive Salt Taste Receptor by Intracellular Ca²⁺, Protein Kinase C, and Calcineurin