CO2 chemosensing in rat oesophagus.
CO2 chemosensing in rat oesophagus.
复制标题
DOI：
10.1136/gut.2007.144378
复制
发表时间：
2008-12
期刊：
影响因子：
24.5
通讯作者：
Kaunitz JD
中科院分区：
文献类型：
--
作者：
Akiba Y;Mizumori M;Kuo M;Ham M;Guth PH;Engel E;Kaunitz JD
食管腔内的酸通常会导致胃灼热。据推测，腔内 CO2（一种渗透气体）而不是 H+ 渗透过上皮细胞，并转化为 H+，通过激活化学传感器产生传入神经信号。大鼠下食管粘膜灌注 pH 7.0 缓冲液和 pH 1.0 或 pH 6.4 高 CO2 (PCO2 = 260 Torr) 溶液，含或不含细胞渗透性碳酸酐酶 (CA) 抑制剂醋甲唑胺 (MTZ, 1 mM)、细胞非渗透性 CA 抑制剂苯甲酰胺 (BNZ, 0.1 mM)、瞬时受体电位香草酸 1 (TRPV1) 拮抗剂辣椒西平 (CPZ，0.5 mM) 或酸敏感离子通道 (ASIC) 抑制剂阿米洛利 (0.1 mM)。将 5',6'-羧基荧光素（静脉注射 5 mg/kg）加载到组织间隙中，测量组织间 pH（pHint），并使用激光多普勒测量血流量。高 CO2 溶液的灌注会在不改变 pHint 的情况下引起充血，模拟 pH 1.0 灌注的效果。灌注 MTZ、BNZ、CPZ 和阿米洛利均能抑制 CO2 诱导的充血。 CA XIV 在棘细胞中表达，CA XII 在基底细胞中表达。 TRPV1 在颗粒层和粘膜肌层中表达，而所有 ASIC 在棘细胞中表达，ASIC3 在粘膜肌层中也表达。对 CO2 灌注的反应表明 CO2 通过上皮层扩散，与上皮或粘膜下层中的 TRPV1 和 ASIC 相互作用。 CA、TRPV1 和 ASIC 抑制剂对腔内 CO2 充血反应的抑制表明 CA 和这些化学传感器参与腔内酸信号的转导。跨上皮 CO2 渗透可以解释管腔 H+ 当量如何快速转变成充血和胃灼热感。
Acid in the oesophageal lumen is often sensed as heartburn. It was hypothesised that luminal CO2, a permeant gas, rather than H+, permeates through the epithelium, and is converted to H+, producing an afferent neural signal by activating chemosensors. The rat lower oesophageal mucosa was superfused with pH 7.0 buffer, and pH 1.0 or pH 6.4 high CO2 (PCO2 = 260 Torr) solutions with or without the cell-permeant carbonic anhydrase (CA) inhibitor methazolamide (MTZ, 1 mM), the cell-impermeant CA inhibitor benzolamide (BNZ, 0.1 mM), the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine (CPZ, 0.5 mM) or the acid-sensing ion channel (ASIC) inhibitor amiloride (0.1 mM). Interstitial pH (pHint) was measured with 5′,6′-carboxyfluorescein (5 mg/kg intravenously) loaded into the interstitial space, and blood flow was measured with laser-Doppler. Perfusion of a high CO2 solution induced hyperaemia without changing pHint, mimicking the effect of pH 1.0 perfusion. Perfused MTZ, BNZ, CPZ and amiloride all inhibited CO2-induced hyperaemia. CA XIV was expressed in the prickle cells, with CA XII in the basal cells. TRPV1 was expressed in the stratum granulosum and in the muscularis mucosa, whereas all ASICs were expressed in the prickle cells, with ASIC3 additionally in the muscularis mucosa. The response to CO2 perfusion suggests that CO2 diffuses through the stratum epithelium, interacting with TRPV1 and ASICs in the epithelium or in the submucosa. Inhibition of the hyperaemic response to luminal CO2 by CA, TRPV1 and ASIC inhibitors implicates CA and these chemosensors in transduction of the luminal acid signal. Transepithelial CO2 permeation may explain how luminal H+ equivalents can rapidly be transduced into hyperaemia, and the sensation of heartburn.