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.

TRPP2 Enhances Metastasis by Regulating Epithelial-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma

“…The results are expressed as the mean cell count of the four fields. ] i was measured using methods described elsewhere [13]. Briefly, the seeded Hep2 cells were loaded with 10 μmol/L Fluo-8 (Invitrogen, USA) with 0.02% pluronic acid F-127 (Sigma-Aldrich Co., USA) at 37 °C for 30 min.…”

“…However, the TRPP2 and PKD1 complex can exert its effect on the kidney epithelium in the pathway that controls epithelial proliferation, differentiation and apoptosis via regulating intracellular Ca 2+ [7]. TRPP2 is not only identified as a likely mutant target responsible for autosomal dominant polycystic kidney disease (ADPKD), but also widely expressed in various cells and participates in many activities relating to proliferation and differentiation, such as those involved in Alzheimer's disease, myocardial hypertrophy, arterial hypertension, and tumour formation [5,[8][9][10][11][12][13].…”

Role of TRPP2 in mouse airway smooth muscle tension and respiration

“…The transient receptor potential polycystic 2 (TRPP2, also known as polycystin-2, PC2, or PKD2) is a pivotal member of the mammalian transient receptor potential superfamily of channel proteins (5,27). TRPP2 is widely expressed in various tissues, including several types of smooth muscle cells, such as those in cerebral arteries, mesenteric arteries, the aorta, the gallbladder, and airway (6,7,22,24,29,34). The TRPP2 protein forms six transmembrane segments with an endoplasmic reticulum (ER) retention signal in the COOH-terminal domain and interacts with numerous proteins, mainly including cytoskeletal components (7,19).…”

TRP Channels as Molecular Targets to Relieve Endocrine-Related Diseases

“…It has been shown that TRPP2 channels are widely distributed in the plasma membrane and endoplasmic reticulum (ER) ( Tsiokas, 2009 ). Xingguo et al found that knockdown of TRPP2 protein in GBSM of guinea pigs significantly decreased Ca 2+ release and extracellular Ca 2+ influx evoked by carnosine (CCh), thereby inhibiting endothelin-1 (ET-1) and cholecystokinin-induced gallbladder contraction ( Zhong et al, 2016 ). Cholecystokinin (CCK) and ET-1 receptors play an important role in GBSM contraction.…”