The role of TRPP2 in agonist-induced gallbladder smooth muscle contraction
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- 作者：Xingguo Zhong ; Jie Fu ; Kai Song ; Nairui Xue ; Renhua Gong…
- 刊名：Science China Life Sciences
- 出版年：2016
- 出版时间：April 2016
- 年：2016
- 卷：59
- 期：4
- 页码：409-416
- 全文大小：832 KB
- 刊物主题：Life Sciences, general;
- 出版者：Springer Berlin Heidelberg
- ISSN：1869-1889
- 卷排序：59
文摘
TRPP2 channel protein belongs to the superfamily of transient receptor potential (TRP) channels and is widely expressed in various tissues, including smooth muscle in digestive gut. Accumulating evidence has demonstrated that TRPP2 can mediate Ca2+ release from Ca2+ stores. However, the functional role of TRPP2 in gallbladder smooth muscle contraction still remains unclear. In this study, we used Ca2+ imaging and tension measurements to test agonist-induced intracellular Ca2+ concentration increase and smooth muscle contraction of guinea pig gallbladder, respectively. When TRPP2 protein was knocked down in gallbladder muscle strips from guinea pig, carbachol (CCh)-evoked Ca2+ release and extracellular Ca2+ influx were reduced significantly, and gallbladder contractions induced by endothelin 1 and cholecystokinin were suppressed markedly as well. CCh-induced gallbladder contraction was markedly suppressed by pretreatment with U73122, which inhibits phospholipase C to terminate inositol 1,4,5-trisphosphate receptor (IP3) production, and 2-aminoethoxydiphenyl borate (2APB), which inhibits IP3 recepor (IP3R) to abolish IP3R-mediated Ca2+ release. To confirm the role of Ca2+ release in CCh-induced gallbladder contraction, we used thapsigargin (TG)-to deplete Ca2+ stores via inhibiting sarco/endoplasmic reticulum Ca2+-ATPase and eliminate the role of store-operated Ca2+ entry on the CCh-induced gallbladder contraction. Preincubation with 2 μmol L-1 TG significantly decreased the CCh-induced gallbladder contraction. In addition, pretreatments with U73122, 2APB or TG abolished the difference of the CCh-induced gallbladder contraction between TRPP2 knockdown and control groups. We conclude that TRPP2 mediates Ca2+ release from intracellular Ca2+ stores, and has an essential role in agonist-induced gallbladder muscle contraction.KeywordsTRP channelTRPP2contractiongallbladder smooth muscleCa2+ storeinositol 1,4,5-trisphosphate receptor