Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction.
Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction.
复制标题
气道平滑肌上的苦味受体通过局部钙信号传导和反向阻塞来支气管扩张。
作者：
舌头的苦味受体（TAS 2 R）可能进化为引起避免摄入植物毒素的信号。我们发现TAS 2 Rs在人气道平滑肌（ASM）上表达，并认为这些是吸入剂的回避受体，导致ASM收缩和支气管痉挛。TAS 2 R激动剂如糖精、氯喹和地那铵以Gβγ、PLCβ和IP 3受体依赖性方式诱发ASM [Ca 2 +]i增加，这是预期的（如乙酰胆碱）诱发收缩。有趣的是，促苦味剂引起分离的ASM松弛，以及比β-激动剂大3倍的气道扩张。TAS 2 R的舒张来自细胞膜上的局部[Ca 2 +]i响应，其打开BKCa通道，导致ASM膜超极化。吸入苦味促味剂减少哮喘小鼠模型的气道阻塞。考虑到需要有效的支气管扩张剂来治疗阻塞性肺病，可以利用该途径来用数千种已知的合成和天然存在的促苦味剂进行治疗。
Bitter taste receptors (TAS2Rs) of the tongue likely evolved to evoke signals for avoiding ingestion of plant toxins. We found expression of TAS2Rs on human airway smooth muscle (ASM) and considered these to be avoidance receptors for inhalants, leading to ASM contraction and bronchospasm. TAS2R agonists such as saccharin, chloroquine and denatonium evoked increased ASM [Ca2+]i in a Gβγ, PLCβ and IP3-receptor dependent manner which would be expected (like acetylcholine) to evoke contraction. Paradoxically, bitter tastants caused relaxation of isolated ASM, and dilation of airways that was 3-fold greater than β-agonists. Relaxation by TAS2Rs is from a localized [Ca2+]i response at the cell membrane which opens BKCa channels leading to ASM membrane hyperpolarization. Inhaled bitter tastants decreased airway obstruction in an asthma mouse model. Given the need for efficacious bronchodilators for treating obstructive lung diseases, this pathway can be exploited for therapy with the thousands of known synthetic and naturally occurring bitter tastants.
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影响因子：
6.7
作者：
Drazen, JM;Silverman, EK;Lee, TH
通讯作者：
Lee, TH
影响因子：
64.5
作者：
Adler, E;Hoon, MA;Zuker, CS
通讯作者：
Zuker, CS
影响因子：
15.9
作者：
McGraw, DW;Mihlbachler, KA;Liggett, SB
通讯作者：
Liggett, SB
影响因子：
--
作者：
Baxter, DF;Kirk, M;Xie, Y
通讯作者：
Xie, Y
DOI：
10.1002/ar.20866
发表时间：
2009-03-01
影响因子：
2
作者：
Sbarbati, Andrea;Tizzano, Marco;Osculati, Francesco
通讯作者：
Osculati, Francesco