The role of epithelial P2Y2 and P2Y4 receptors in the regulation of intestinal chloride secretion
The role of epithelial P2Y2 and P2Y4 receptors in the regulation of intestinal chloride secretion
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DOI：
10.1038/sj.bjp.0706353
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发表时间：
2005-10-01
影响因子：
7.3
通讯作者：
Boeynaems, JM
中科院分区：
文献类型：
--
作者：
Ghanem, E;Robaye, B;Boeynaems, JM
1 utp诱导的氯离子分泌由安装在Ussing腔内的肠粘膜进行评估，通过测量空肠中有苯丙素或结肠中有阿米洛利时的短路电流（I-sc）来消除任何电致Na+运动对净离子运输的贡献。由于我们之前已经证明P2Y(4)-缺失小鼠空肠对根尖UTP没有氯化物分泌反应，在本研究中，我们研究了P2Y(2)-和P2Y(4)-缺失小鼠空肠对基底外侧UTP的反应，以及结肠对根尖或基底外侧UTP的反应在空肠中，P2Y(2)-(40%)和P2Y(4)-(60%)缺失小鼠对基底外侧UTP的氯化物分泌反应部分降低在结肠，根尖或基底外侧UTP均增加I-sc。这种反应在无氯化物介质中消失在P2Y(4)缺陷小鼠中，结肠对基底外侧或根尖UTP的氯分泌反应被消除，但在P2Y(2)缺陷小鼠中没有明显影响。对福斯克林的氯化物分泌反应可以通过事先在基底外侧添加UTP而增强，而这种增强作用在P2Y(4)-缺失的小鼠中被消除囊性纤维化跨膜传导调节因子δ F508突变纯合子小鼠空肠对UTP有反应，但反应幅度小于野生型小鼠综上所述，P2Y(4)受体完全介导小肠和大肠对UTP的氯化物分泌反应，但在空肠基底外侧，P2Y(2)和P2Y(4)受体均参与。
1 UTP-induced chloride secretion by the intestinal mucosa mounted in Ussing chambers was assessed by measurement of the short-circuit current (I-sc) in the presence of phloridzin in the case of jejunum or amiloride in the case of colon to eliminate any contribution of electrogenic Na+ movement to the net ionic transport. Since we have previously demonstrated the absence of chloride-secretory response to apical UTP in the jejunum from P2Y(4)-null mice, in the present study we studied the response to basolateral UTP in the jejunum and to either apical or basolateral UTP in the colon, in both P2Y(2)- and P2Y(4)-deficient mice.2 In the jejunum, the chloride-secretory response to basolateral UTP was partially reduced in both P2Y(2)- (40%) and P2Y(4)- (60%) null mice.3 In the colon, both apical or basolateral UTP increased the I-sc. That response was abolished in a chloride-free medium.4 The colonic chloride-secretory response to either basolateral or apical UTP was abolished in P2Y(4)-deficient mice, but not significantly affected in P2Y(2)- deficient mice. The chloride-secretory response to forskolin was potentiated by prior basolateral addition of UTP and this potentiation was abolished in P2Y(4)- null mice.5 The jejunum of mice homozygous for the Delta F508 mutation of cystic fibrosis transmembrane conductance regulator was responsive to UTP, but the magnitude of that response was smaller than in the wild-type littermates.6 In conclusion, the P2Y(4) receptor fully mediates the chloride-secretory response to UTP in both small and large intestines, except at the basolateral side of the jejunum, where both P2Y(2) and P2Y(4) receptors are involved.