PMID- 26660312 OWN - NLM STAT- MEDLINE DCOM- 20170111 LR - 20170112 IS - 1869-1889 (Electronic) IS - 1674-7305 (Linking) VI - 59 IP - 4 DP - 2016 Apr TI - The role of TRPP2 in agonist-induced gallbladder smooth muscle contraction. PG - 409-16 LID - 10.1007/s11427-015-4958-5 [doi] AB - 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 Ca(2+) release from Ca(2+) stores. However, the functional role of TRPP2 in gallbladder smooth muscle contraction still remains unclear. In this study, we used Ca(2+) imaging and tension measurements to test agonist-induced intracellular Ca(2+) 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 Ca(2+) release and extracellular Ca(2+) 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 Ca(2+) release. To confirm the role of Ca(2+) release in CCh-induced gallbladder contraction, we used thapsigargin (TG)-to deplete Ca(2+) stores via inhibiting sarco/endoplasmic reticulum Ca(2+)-ATPase and eliminate the role of store-operated Ca(2+) entry on the CCh-induced gallbladder contraction. Preincubation with 2 mumol 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 Ca(2+) release from intracellular Ca(2+) stores, and has an essential role in agonist-induced gallbladder muscle contraction. FAU - Zhong, Xingguo AU - Zhong X AD - Department of Surgery, Anhui Provincial Corps Hospital of Chinese People's Armed Police Force, Heifei, 230041, China. FAU - Fu, Jie AU - Fu J AD - Department of Physiology, Anhui Medical University, Heifei, 230032, China. FAU - Song, Kai AU - Song K AD - Department of Physiology, Anhui Medical University, Heifei, 230032, China. FAU - Xue, Nairui AU - Xue N AD - Department of Physiology, Anhui Medical University, Heifei, 230032, China. FAU - Gong, Renhua AU - Gong R AD - Department of Surgery, Anhui Provincial Corps Hospital of Chinese People's Armed Police Force, Heifei, 230041, China. FAU - Sun, Dengqun AU - Sun D AD - Department of Surgery, Anhui Provincial Corps Hospital of Chinese People's Armed Police Force, Heifei, 230041, China. FAU - Luo, Huilai AU - Luo H AD - Department of Surgery, Anhui Provincial Corps Hospital of Chinese People's Armed Police Force, Heifei, 230041, China. FAU - He, Wenzhu AU - He W AD - Department of Physiology, Anhui Medical University, Heifei, 230032, China. FAU - Pan, Xiang AU - Pan X AD - Department of Physiology, Anhui Medical University, Heifei, 230032, China. FAU - Shen, Bing AU - Shen B AD - Department of Physiology, Anhui Medical University, Heifei, 230032, China. shenbing@ahmu.edu.cn. AD - Central Laboratory of Molecular And Cellular Biology of Basic Medical College, Anhui Medical University, Heifei, 230032, China. shenbing@ahmu.edu.cn. FAU - Du, Juan AU - Du J AD - Department of Physiology, Anhui Medical University, Heifei, 230032, China. dujuan@ahmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151211 PL - China TA - Sci China Life Sci JT - Science China. Life sciences JID - 101529880 RN - 0 (Cholinergic Agonists) RN - 0 (Endothelin-1) RN - 0 (Enzyme Inhibitors) RN - 0 (Estrenes) RN - 0 (Inositol 1,4,5-Trisphosphate Receptors) RN - 0 (Phosphodiesterase Inhibitors) RN - 0 (Pyrrolidinones) RN - 0 (TRPP Cation Channels) RN - 0 (polycystic kidney disease 2 protein) RN - 112648-68-7 (1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione) RN - 67526-95-8 (Thapsigargin) RN - 8Y164V895Y (Carbachol) RN - 9011-97-6 (Cholecystokinin) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Blotting, Western MH - Calcium/metabolism MH - Carbachol/pharmacology MH - Cholecystokinin/pharmacology MH - Cholinergic Agonists/pharmacology MH - Endothelin-1/pharmacology MH - Enzyme Inhibitors/pharmacology MH - Estrenes/pharmacology MH - Gallbladder/*physiology MH - Guinea Pigs MH - In Vitro Techniques MH - Inositol 1,4,5-Trisphosphate Receptors/metabolism MH - Intracellular Space/metabolism MH - Male MH - Models, Biological MH - Muscle Contraction/drug effects/*physiology MH - Muscle, Smooth/*physiology MH - Phosphodiesterase Inhibitors/pharmacology MH - Pyrrolidinones/pharmacology MH - RNA Interference MH - TRPP Cation Channels/genetics/metabolism/*physiology MH - Thapsigargin/pharmacology OTO - NOTNLM OT - Ca2+ store OT - TRP channel OT - TRPP2 OT - contraction OT - gallbladder smooth muscle OT - inositol 1,4,5-trisphosphate receptor EDAT- 2015/12/15 06:00 MHDA- 2017/01/12 06:00 CRDT- 2015/12/15 06:00 PHST- 2015/07/26 00:00 [received] PHST- 2015/09/01 00:00 [accepted] PHST- 2015/12/15 06:00 [entrez] PHST- 2015/12/15 06:00 [pubmed] PHST- 2017/01/12 06:00 [medline] AID - 10.1007/s11427-015-4958-5 [pii] AID - 10.1007/s11427-015-4958-5 [doi] PST - ppublish SO - Sci China Life Sci. 2016 Apr;59(4):409-16. doi: 10.1007/s11427-015-4958-5. Epub 2015 Dec 11.