title: The role of TRPP2 in agonist-induced gallbladder smooth muscle contraction.
abstract: 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 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 Ca(2+) release from intracellular Ca(2+) stores, and has an essential role in agonist-induced gallbladder muscle contraction.
authors.affiliation: Department of Surgery, Anhui Provincial Corps Hospital of Chinese People's Armed Police Force, Heifei, 230041, China.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Physiology, Anhui Medical University, Heifei, 230032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Physiology, Anhui Medical University, Heifei, 230032, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Physiology, Anhui Medical University, Heifei, 230032, China.
authors.forename: Nairui
authors.initials: N
authors.lastname: Xue
authors.affiliation: Department of Surgery, Anhui Provincial Corps Hospital of Chinese People's Armed Police Force, Heifei, 230041, China.
authors.forename: Renhua
authors.initials: R
authors.lastname: Gong
authors.affiliation: Department of Surgery, Anhui Provincial Corps Hospital of Chinese People's Armed Police Force, Heifei, 230041, China.
authors.forename: Dengqun
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Surgery, Anhui Provincial Corps Hospital of Chinese People's Armed Police Force, Heifei, 230041, China.
authors.forename: Huilai
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Physiology, Anhui Medical University, Heifei, 230032, China.
authors.forename: Wenzhu
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Physiology, Anhui Medical University, Heifei, 230032, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Physiology, Anhui Medical University, Heifei, 230032, China. shenbing@ahmu.edu.cn.|Central Laboratory of Molecular And Cellular Biology of Basic Medical College, Anhui Medical University, Heifei, 230032, China. shenbing@ahmu.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Physiology, Anhui Medical University, Heifei, 230032, China. dujuan@ahmu.edu.cn.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005704:Gallbladder / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D034622:RNA Interference; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002118:Calcium; D002217:Carbachol; D002766:Cholecystokinin; D018679:Cholinergic Agonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D004963:Estrenes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D050396:TRPP Cation Channels; D019284:Thapsigargin; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
keywords: Ca2+ store; TRP channel; TRPP2; contraction; gallbladder smooth muscle; inositol 1,4,5-trisphosphate receptor