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"Calcium sensing receptor"

Alamuddin Bakhit, Nobuyuki Kawashima, Kentaro Hashimoto, Sonoko Noda, Keisuke Nara, Masashi Kuramoto, Kento Tazawa, Takashi Okiji
This study examined the effects and mechanisms of strontium ranelate (SrRn)-a drug used to treat osteoporosis-on the proliferation and differentiation/mineralization of cloned dental pulp-like cells (mouse dental papillae cells; MDPs). It also determined whether topical application of SrRn to exposed dental pulp tissue promotes the formation of mineralized tissue in vivo. The MDPs were cultured with or without SrRn, and cell proliferation, odonto-/osteoblastic gene expression, mineralized nodule formation, and Akt phosphorylation were evaluated...
June 15, 2018: Scientific Reports
E Mogas, A Campos-Martorell, M Clemente, L Castaño, A Moreno-Galdó, D Yeste, A Carrascosa
Two pediatric patients with different causes of hyperparathyroidism are reported. First patient is a 13-year-old male with severe hypercalcemia due to left upper parathyroid gland adenoma. After successful surgery, calcium and phosphate levels normalized, but parathormone levels remained elevated. Further studies revealed a second adenoma in the right gland. The second patient is a 13-year-old female with uncommon hypercalcemia symptoms. Presence of pathogenic calcium-sensing receptor gene ( CASR ) mutation was found, resulting in diagnosis of symptomatic familial hypocalciuric hypercalcemia...
2018: Endocrinology, Diabetes & Metabolism Case Reports
Li-Yih Lin, Ya-Hsin Yeh, Giun-Yi Hung, Chia-Hao Lin, Pung-Pung Hwang, Jiun-Lin Horng
The calcium-sensing receptor (CaSR) is an extracellular Ca2+ sensor that plays a critical role in maintaining Ca2+ homeostasis in several organs, including the parathyroid gland and kidneys. In this study, through in situ hybridization, the expression of CaSR mRNA was found in the neuromasts of zebrafish larvae. Immunohistochemistry further demonstrated that the CaSR protein was present in neuromast hair cell stereocilia and basolateral membranes. Based on the expression and subcellular localization of the CaSR in hair cells, we hypothesized that the CaSR is expressed in zebrafish lateral-line hair cells to regulate mechanotransducer (MET)-channel-mediated Ca2+ entry...
2018: Frontiers in Physiology
Yoko Ueda, Hiroshi Iwakura, Mika Bando, Asako Doi, Hiroyuki Ariyasu, Hidefumi Inaba, Shuhei Morita, Takashi Akamizu
Tryptophan is reportedly the most potent agonist for GPR142. Glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells are enhanced by GPR142-mediated signal. It is not clear, however, if GPR142-mediated signals is solely attributable to GSIS enhancement after tryptophan load in various pathophysiological settings. This study aims to reveal the significance of GPR142 signaling in tryptophan-mediated GSIS enhancement in normal and obese mice. Tryptophan significantly improved glucose tolerance in both lean and DIO mice, but the extent of improvement was bigger in DIO mice with augmented glucose-stimulated insulin secretion (GSIS) enhancement...
2018: PloS One
Junichiro James Kazama, Minako Wakasugi
Bone maintains extracellular calcium levels through a system called bone remodeling. Parathyroid hormone (PTH) is the major initiator of this system, which is secreted by the information through calcium sensing receptor in parathyroid cells. PTH modifies calcified bone morphology through a process of its bone action. Therefore, extremely hyperactivated parathyroid function seen in patients with chronic kidney disease has been considered to have a negative impact on the bone mechanical properties. While skeletal deformities and fragility fractures were common among dialysis patients up to the 1970s, after which methods for the treatment of hyperparathyroidism were developed, we now seldom encounter those cases with severe secondary hyperparathyroidism in Japan...
June 2018: Therapeutic Apheresis and Dialysis
Enikö Kallay
No abstract text is available yet for this article.
2018: Frontiers in Physiology
Wuhua Zhou, Li Gong, Xuefeng Li, Yunyan Wan, Xiangfei Wang, Huili Li, Bin Jiang
Insulinoma is a rare type tumor and its genetic features remain largely unknown. This study aimed to search for potential key genes and relevant enriched pathways of insulinoma.The gene expression data from GSE73338 were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified between insulinoma tissues and normal pancreas tissues, followed by pathway enrichment analysis, protein-protein interaction (PPI) network construction, and module analysis. The expressions of candidate key genes were validated by quantitative real-time polymerase chain reaction (RT-PCR) in insulinoma tissues...
June 2018: Medicine (Baltimore)
Silvana Bazúa-Valenti, Lorena Rojas-Vega, María Castañeda-Bueno, Jonatan Barrera-Chimal, Rocío Bautista, Luz G Cervantes-Pérez, Norma Vázquez, Consuelo Plata, Adrián R Murillo-de-Ozores, Lorenza González-Mariscal, David H Ellison, Daniela Riccardi, Norma A Bobadilla, Gerardo Gamba
Background Hypercalciuria can result from activation of the basolateral calcium-sensing receptor (CaSR), which in the thick ascending limb of Henle's loop controls Ca2+ excretion and NaCl reabsorption in response to extracellular Ca2+ However, the function of CaSR in the regulation of NaCl reabsorption in the distal convoluted tubule (DCT) is unknown. We hypothesized that CaSR in this location is involved in activating the thiazide-sensitive NaCl cotransporter (NCC) to prevent NaCl loss. Methods We used a combination of in vitro and in vivo models to examine the effects of CaSR on NCC activity...
May 30, 2018: Journal of the American Society of Nephrology: JASN
Glynis B Mattheisen, Timur Tsintsadze, Stephen M Smith
Voltage-gated sodium channels (VGSCs) are strategically positioned to mediate neuronal plasticity because of their influence on action potential waveform. VGSC function may be strongly inhibited by local anesthetic and antiepileptic drugs and modestly modulated via second messenger pathways. Here, we report that the allosteric modulators of the calcium-sensing receptor (CaSR) cinacalcet, calindol, calhex, and NPS 2143 completely inhibit VGSC current in the vast majority of cultured mouse neocortical neurons...
May 29, 2018: Cell Reports
Branca M Cavaco, Lucie Canaff, Alexis Nolin-Lapalme, Margarida Vieira, Tiago Silva, Ana Saramago, Rita Domingues, Meilan M Rutter, Jonathan Hudon, James L Gleason, Valeriano Leite, Geoffrey N Hendy
Context: Autosomal dominant hypocalcemia type 1 is caused by heterozygous activating mutations in the calcium-sensing receptor gene (CASR). Whether polymorphisms that are benign in the heterozygous state pathologically alter receptor function in the homozygous state is not known. Objective: To identify the genetic defect in an adolescent female with a past history of surgery for bilateral cataracts and seizures. The patient has hypocalcemia, hyperphosphatemia and low serum parathyroid hormone (PTH) levels...
May 25, 2018: Journal of Clinical Endocrinology and Metabolism
Antonela Matana, Marijana Popović, Vesela Torlak, Ante Punda, Maja Barbalić, Tatijana Zemunik
BACKGROUND: Parathyroid hormone (PTH) is one of the principal regulators of calcium homeostasis, crucial for normal functioning of the kidneys, bones, heart, and nervous system. Different pathologic conditions can affect serum PTH level resulting in hyperparathyroidism or hypoparathyroidism. Our study assessed the association of previously reported polymorphisms with the level of PTH (expressed in pg/mL) among individuals with different pathologic conditions affecting PTH level. METHODS: We searched Web of Science, MEDLINE, and Scopus to identify relevant articles published up to July 2017...
May 2018: Medicine (Baltimore)
Yihan Xian, Xiuying Zhao, Chao Wang, Cuicui Kang, Liren Ding, Weiyun Zhu, Suqin Hang
In rodents and humans, aromatic amino acids increase gut hormone secretion and H+ -K+ -ATPase activity by modulating calcium-sensing receptor (CaSR). However, the role of CaSR and its related signaling molecules in amino acid-induced gut hormone secretion in swine has not been investigated. Here, we examined whether a CaSR-dependent pathway modulated gastrin and somatostatin (SS) secretion and H+ -K+ -ATPase activity in pigs. Perfusion of pig stomach tissues in the presence of extracellular 80 mM l-phenylalanine (Phe) or 20 mM l-tryptophan (Trp) and a CaSR agonist cinacalcet triggered gastrin and SS secretion and H+ -K+ -ATPase activity (P < 0...
May 18, 2018: General and Comparative Endocrinology
Lieqi Tang, Lingli Jiang, Megan E McIntyre, Ekaterina Petrova, Sam X Cheng
Treatment of acute secretory diarrheal illnesses remains a global challenge. Enterotoxins produce secretion through direct epithelial action and indirectly by activating enteric nervous system (ENS). Using a microperfused colonic crypt technique, we have previously shown that R568, a calcimimetic that activates the calcium-sensing receptor (CaSR), can act on intestinal epithelium and reverse cholera toxin-induced fluid secretion. In the present study, using the Ussing chamber technique in conjunction with a tissue-specific knockout approach, we show that the effects of cholera toxin and CaSR agonists on electrolyte secretion by the intestine can also be attributed to opposing actions of the toxin and CaSR on the activity of the ENS...
May 18, 2018: Scientific Reports
Sousuke Kanaya, Binlu Xiao, Yukihiko Sakisaka, Mizuki Suto, Kentaro Maruyama, Masahiro Saito, Eiji Nemoto
We previously reported that elevated extracellular calcium (Ca2+) levels increase bone morphogenetic protein 2 expression in human dental pulp (hDP) cells. However, it is unknown whether extracellular Ca2+ affects the expression of other growth factors such as fibroblast growth factor 2 (FGF2). The present study aimed to examine the effect of extracellular Ca2+ on FGF2 gene expression in hDP and immortalized mouse dental papilla (mDP) cells. Cells were stimulated with 10 mM CaCl2 in the presence or absence of cell signaling inhibitors...
May 14, 2018: Journal of Applied Oral Science: Revista FOB
Alicja E Grzegorzewska, Dariusz Bednarski, Monika Świderska, Adrianna Mostowska, Paweł P Jagodziński
BACKGROUND/AIMS: The calcium-sensing receptor gene (CASR) rs1801725 variant is responsible for a non-conservative amino-acid change (A986S) in the calcium-sensing receptor cytoplasmic tail. We hypothesized that rs1801725 polymorphism might be helpful in understanding Ca-related abnormalities in HD patients. METHODS: In 1215 subjects (245 on cinacalcet), we determined the associations of rs1801725 with secondary hyperparathyroidism (sHPT)-related laboratory parameters, PTH-decreasing effect of cinacalcet hydrochloride, coronary artery disease (CAD), myocardial infarction (MI), nephrolithiasis-related ESRD, and mortality...
May 10, 2018: Kidney & Blood Pressure Research
Anne Qvist Rasmussen, Niklas Rye Jørgensen, Peter Schwarz
The human calcium-sensing receptor ( CASR ) is the key controller of extracellular Cao 2+ homeostasis, and different mutations in the CASR gene have been linked to different calcium diseases, such as familial hypocalciuric hypercalcemia, severe hyperparathyroidism, autosomal-dominant hypocalcemia (ADH), and Bartter's syndrome type V. In this study, two generations of a family with biochemically and clinically confirmed ADH who suffered severe muscle pain, arthralgia, tetany, abdominal pain, and fatigue were evaluated for mutations in the CASR gene...
2018: Frontiers in Endocrinology
Hiroshi Miyazaki, Yousuke Ikeda, Osamu Sakurai, Tsutomu Miyake, Rie Tsubota, Jyunko Okabe, Masataka Kuroda, Yutaka Hisada, Tetsuya Yanagida, Hikaru Yoneda, Yukihito Tsukumo, Shin Tokunaga, Takehisa Kawata, Rikiya Ohashi, Hajime Fukuda, Koki Kojima, Ayako Kannami, Takayuki Kifuji, Naoya Sato, Akiko Idei, Taku Iguchi, Tetsuya Sakairi, Yasunori Moritani
The calcium-sensing receptor (CaSR) plays an important role in sensing extracellular calcium ions and regulating parathyroid hormone secretion by parathyroid gland cells, and the receptor is a suitable target for the treatment of hyperparathyroidism. Cinacalcet hydrochloride is a representative CaSR agonist which widely used for the hyperparathyroidism. However, it has several issues to clinical use, such as nausea/vomiting and strong inhibition of CYP2D6. We tried to improve these issues of cinacalcet for a new pharmaceutical agent as a preferable CaSR agonist...
April 24, 2018: Bioorganic & Medicinal Chemistry Letters
Natalie A Diepenhorst, Katie Leach, Andrew N Keller, Patricia Rueda, Anna E Cook, Tracie L Pierce, Cameron Nowell, Philippe Pastoureau, Massimo Sabatini, Roger J Summers, William N Charman, Patrick M Sexton, Arthur Christopoulos, Christopher J Langmead
BACKGROUND AND PURPOSE: Strontium ranelate, a drug approved, and until recently used for the treatment of osteoporosis, mediates its effects on bone at least in part via the calcium-sensing receptor (CaSR). However, it is not known whether bone-targeted CaSR positive allosteric modulators (PAMs; calcimimetics) represent an alternative (or adjunctive) therapy to strontium (Sr2+ o ). EXPERIMENTAL APPROACH: We assessed three structurally distinct calcimimetics (cinacalcet, AC-265347 and a benzothiazole tri-substituted urea [BTU-compound 13]), alone and in combination with extracellular calcium (Ca2+ o ) or Sr2+ o , in G protein-dependent signalling assays and trafficking experiments in HEK293 cells and for their effects on cell differentiation, tartrate-resistant alkaline phosphatase (TRAP) activity and hydroxyapatite resorption assays in human blood-derived osteoclasts...
May 1, 2018: British Journal of Pharmacology
Yansu Ji, Tianqi Wang, Xiting Zhang, Lailai Li, Liang Li, Yisha Guo, Bo Yang, Yi Wang, Tieliang Zhu
This study was designed to investigate the effects of astragalosides on cardiac diastolic function, and an emphasis was placed on the variation of the upstream molecular regulators of phospholamban. Chronic heart failure (CHF) rats were induced by ligaturing the left anterior coronary artery, and rats in the therapeutic groups were treated with either a 50 mg/kg dose of captopril, 10 mg/kg dose of astragalosides or 20 mg/kg dose of astragalosides. Four weeks after treatment, the ratio of the early and atrial peak filling velocities (E/A) and maximal slope diastolic pressure decrement (-dp/dt) both decreased in CHF rats (by 30...
April 21, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
R F Geddes, R E Jepson, Y Forcada, J Elliott, H M Syme
Feline chronic kidney disease (CKD) is associated with high variability in severity of CKD-mineral and bone disorder (CKD-MBD). The calcium sensing receptor (CaSR) regulates circulating parathyroid hormone (PTH) and calcium concentrations. Single nucleotide polymorphisms (SNPs) in the CaSR are associated with severity of secondary renal hyperparathyroidism and total calcium concentrations in human patients receiving haemodialysis. The objective of this study was to explore associations between polymorphisms in the feline CaSR (fCaSR) and biochemical changes observed in CKD-MBD...
May 2018: Veterinary Journal
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