Lyall Vijay, Heck Gerard L, Phan Tam-Hao T, Mummalaneni Shobha, Malik Shahbaz A, Vinnikova Anna K, Desimone John A
Department of Physiology, Division of Nephrology, Virginia Commonwealth University, Richmond, VA 23298, USA.
J Gen Physiol. 2005 Jun;125(6):587-600. doi: 10.1085/jgp.200509264.
The effect of ethanol on the amiloride- and benzamil (Bz)-insensitive salt taste receptor was investigated by direct measurement of intracellular Na(+) activity (Na(+)) 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.
通过使用荧光成像技术直接测量极化的菌状味觉受体细胞（TRCs）中的细胞内钠离子活性（[Na⁺]i），以及通过鼓索神经（CT）味觉神经记录，研究了乙醇对amiloride和苯扎米（Bz）不敏感的盐味受体的影响。在Sprague-Dawley大鼠、野生型（WT）和香草酸受体-1（VR-1）基因敲除小鼠（KO）中记录了CT对KCl和NaCl的反应。在存在上皮钠离子通道（ENaC）的特异性阻滞剂Bz的情况下监测CT反应。还在VR-1的激动剂（树脂毒素和升高温度）和拮抗剂（辣椒素和SB-366791）存在的情况下记录CT反应，这些物质同样调节Bz不敏感的VR-1变体盐味受体。在无矿物盐的情况下，乙醇导致TRC体积短暂减小，并仅引发短暂的相位性CT反应。在有矿物盐的情况下，乙醇增加了TRCs顶端的阳离子通量，而体积无变化，增加了舌上皮的跨上皮电阻，并引发了类似于盐反应的CT反应，包括一个相位成分和一个持续的紧张成分。在乙醇浓度<50%时，乙醇增强了对KCl和NaCl的反应，而在乙醇浓度>50%时，那些CT反应受到抑制。树脂毒素和升高温度增加了含盐培养基中CT对乙醇反应的敏感性，而SB-366791抑制了乙醇、树脂毒素和升高温度对CT对矿物盐反应的影响。VR-基因敲除小鼠对NaCl没有Bz不敏感的CT反应，对乙醇也不敏感。我们得出结论，乙醇通过直接作用于Bz不敏感的VR-1变体盐味受体来增加盐味敏感性。
