Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23219, USA.
Am J Physiol Gastrointest Liver Physiol. 2013 Jul 1;305(1):G106-17. doi: 10.1152/ajpgi.00053.2013. Epub 2013 May 2.
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 + 5 μM Bz (NaCl + 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 + Bz + 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 + Bz CT response, enhancing the response at 0.5-1 μM and inhibiting it at >1 μM. The NaCl + Bz + SB-366791 CT response in rats and WT mice and the NaCl + 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 + 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 + Bz tonic CT response. The relationship between RTX concentration and the magnitude of the tonic NaCl + 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.
瞬时受体电位（TRP）亚家族 M 成员 5（TRPM5）阳离子通道参与感知甜味、苦味、鲜味和脂肪味道刺激物、口感复杂的二价盐以及甜味的温度诱导变化。为了研究阿米洛利和苯甲脒（Bz）不敏感的氯化钠鼓索（CT）味觉神经反应是否也部分受到 TRPM5 的调节，在辣椒素（RTX）存在的情况下，监测 Sprague-Dawley 大鼠、野生型（WT）小鼠和 TRPV1 和 TRPM5 敲除（KO）小鼠的 CT 对 100 mM NaCl + 5 μM Bz（NaCl + Bz）的反应TRPV1 激动剂。在大鼠中，还监测了 NaCl + Bz + RTX CT 反应在特定的 TRPM5 阻断剂三苯基氧化膦和辣椒素和 N-（3-甲氧基苯基）-4-氯肉桂酰胺（SB-366791），特定 TRPV1 阻断剂存在的情况下。在大鼠和 WT 小鼠中，RTX 对 NaCl + Bz CT 反应产生双相作用，在 0.5-1 μM 时增强反应，在 >1 μM 时抑制反应。在大鼠和 WT 小鼠中，NaCl + Bz + SB-366791 CT 反应和 TRPV1 KO 小鼠中的 NaCl + Bz CT 反应被抑制到基线水平，对 RTX 不敏感。在大鼠中，用辣椒素阻断 TRPV1 或用三苯基氧化膦阻断 TRPM5 抑制了持续的 NaCl + Bz CT 反应，并将 RTX 浓度与持续 CT 反应幅度之间的关系转移到更高的 RTX 浓度。TRPM5 KO 小鼠没有引起组成性的 NaCl + Bz 持续 CT 反应。RTX 浓度与持续的 NaCl + Bz CT 反应幅度之间的关系明显减弱，并转移到更高的 RTX 浓度。结果表明，TRPM5 活性的药理学或遗传改变调节了 Bz 不敏感的 NaCl CT 反应及其对 TRPV1 激动剂的调节。
