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"Calcium sensing receptor"

Hao Li, Jianhua Zhang, Jiang Long, Jiarun Shi, Yuhui Luo
The calcium-sensing receptor (CaSR) gene plays an important role in regulating the Ca2+ balance and reducing the risk for calcium stones. In this study, we evaluated the association of CaSR polymorphisms with calcium nephrolithiasis in the population of Yi nationality in Southwestern China. Biochemical variables were evaluated in 624 calcium nephrolithiasis patients and 470 age-matched healthy controls without a history of nephrolithiasis. CaSR polymorphisms rs7652589, rs1501899, rs1801725 (Ala986Ser), rs1042636 (Arg990Gly) and rs1801726 (Gln1011Glu) were investigated between the calcium nephrolithiasis patients and healthy controls, using direct sequencing...
April 16, 2018: Annals of Human Genetics
Fang He, Chenlu Wu, Pan Li, Nengzhang Li, Dong Zhang, Quoqiang Zhu, Wenkai Ren, Yuanyi Peng
Intestine is always exposed to external environment and intestinal microorganism; thus it is more sensitive to dysfunction and dysbiosis, leading to intestinal inflammation, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and diarrhea. An increasing number of studies indicate that dietary amino acids play significant roles in preventing and treating intestinal inflammation. The review aims to summarize the functions and signaling mechanisms of amino acids in intestinal inflammation...
2018: BioMed Research International
Roshan A Jain, Marc A Wolman, Kurt C Marsden, Jessica C Nelson, Hannah Shoenhard, Fabio A Echeverry, Christina Szi, Hannah Bell, Julianne Skinner, Emilia N Cobbs, Keisuke Sawada, Amy D Zamora, Alberto E Pereda, Michael Granato
Animals continuously integrate sensory information and select contextually appropriate responses. Here, we show that zebrafish larvae select a behavioral response to acoustic stimuli from a pre-existing choice repertoire in a context-dependent manner. We demonstrate that this sensorimotor choice is modulated by stimulus quality and history, as well as by neuromodulatory systems-all hallmarks of more complex decision making. Moreover, from a genetic screen coupled with whole-genome sequencing, we identified eight mutants with deficits in this sensorimotor choice, including mutants of the vertebrate-specific G-protein-coupled extracellular calcium-sensing receptor (CaSR), whose function in the nervous system is not well understood...
April 6, 2018: Current Biology: CB
Aizhan Tastanova, Marc Folcher, Marius Müller, Gieri Camenisch, Aaron Ponti, Thomas Horn, Maria S Tikhomirova, Martin Fussenegger
Diagnosis marks the beginning of any successful therapy. Because many medical conditions progress asymptomatically over extended periods of time, their timely diagnosis remains difficult, and this adversely affects patient prognosis. Focusing on hypercalcemia associated with cancer, we aimed to develop a synthetic biology-inspired biomedical tattoo using engineered cells that would (i) monitor long-term blood calcium concentration, (ii) detect onset of mild hypercalcemia, and (iii) respond via subcutaneous accumulation of the black pigment melanin to form a visible tattoo...
April 18, 2018: Science Translational Medicine
Fei Tong, Rongkui Chai, Haiying Jiang, Bo Dong
Background: The objective of this study was to survey the therapeutic function of curcumin-encapsulated poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gammabenzyl l-glutamate) (PBLG-PEG-PBLG) (P) on diabetic cardiomyopathy (DCM) via cross regulation effect of calcium-sensing receptor (CaSR) and endogenous cystathionine-γ-lyase (CSE)/hydrogen sulfide (H2 S). Methods: Diabetic rats were preconditioned with 20 mg/kg curcumin or curcumin/P complex continuously for 8 weeks...
2018: International Journal of Nanomedicine
Sebastian Frees, Ines Breuksch, Tobias Haber, Heide-Katharina Bauer, Claudia Chavez-Munoz, Peter Raven, Igor Moskalev, Ninadh D Costa, Zheng Tan, Mads Daugaard, Joachim W Thüroff, Axel Haferkamp, Dirk Prawitt, Alan So, Walburgis Brenner
Bone metastasis is an important prognostic factor in renal cell carcinoma (RCC). The calcium-sensing receptor (CaSR) has been associated with bone metastasis in several different malignancies. We analyzed the impact of CaSR in bone metastasis in RCC in vitro and in vivo . The RCC cell line 786-O was stably transfected with the CaSR gene and treated with calcium alone or in combination with the CaSR antagonist NPS2143. Afterwards migration, adhesion, proliferation and prominent signaling molecules were analyzed...
March 20, 2018: Oncotarget
Yi Fan, Weiqing Liu, Ruiye Bi, Michael J Densmore, Tadatoshi Sato, Michael Mannstadt, Quan Yuan, Xuedong Zhou, Hannes Olauson, Tobias E Larsson, Hakan R Toka, Martin R Pollak, Edward M Brown, Beate Lanske
The pathogenesis of parathyroid gland hyperplasia is poorly understood, and a better understanding is essential if there is to be improvement over the current strategies for prevention and treatment of secondary hyperparathyroidism. Here we investigate the specific role of Klotho expressed in the parathyroid glands (PTGs) in mediating parathyroid hormone (PTH) and serum calcium homeostasis, as well as the potential interaction between calcium-sensing receptor (CaSR) and Klotho. We generated mouse strains with PTG-specific deletion of Klotho and CaSR and dual deletion of both genes...
April 4, 2018: Proceedings of the National Academy of Sciences of the United States of America
W J Zang, H Li, Z F Zhang, R QuZhen, Y Z CuoMu, D K Zhang, J Luo, J J Loor, H L Zheng
During lactation, large amounts of calcium are exported from the mammary gland into milk to ensure skeletal growth of the offspring. Recent studies revealed that serotonin (5-HT) is essential to stimulate skeletal calcium resorption for milk synthesis. Our objective was to explore the correlation between circulating 5-HT and serum calcium and parathyroid hormone-related protein (PTHrP) concentrations around parturition in dairy goats. We also investigated the effect of 5-HT on PTHrP expression in cultured primary goat mammary epithelial cells (GMEC)...
April 3, 2018: Journal of Animal Science
Sílvia F Gregório, Juan Fuentes
In marine fish, high epithelial intestinal HCO₃− secretion generates luminal carbonate precipitates of divalent cations that play a key role in water and ion homeostasis. The present study was designed to expose the putative role for calcium and the calcium-sensing receptor (CaSR) in the regulation of HCO₃− secretion in the intestine of the sea bream ( Sparus aurata L.). Effects on the expression of the CaSR in the intestine were evaluated by qPCR and an increase was observed in the anterior intestine in fed fish compared with unfed fish and with different regions of intestine...
April 4, 2018: International Journal of Molecular Sciences
Daisuke Miyatake, Naoyuki Nakada, Akitsugu Takada, Kota Kato, Yuta Taniuchi, Masataka Katashima, Taiji Sawamoto
ASP7991 is a calcimimetic that acts on the calcium-sensing receptor on parathyroid cell membranes and suppresses parathyroid hormone (PTH) secretion in the treatment of secondary hyperparathyroidism. The mass balance and metabolite profile of [14 C]ASP7991 were investigated in six healthy male subjects after a single oral dose of [14 C]ASP7991 [1 mg, 18.5 kBq (500 nCi)] in solution. [14 C] radioactivity in plasma, urine and feces was analyzed using Accelerator mass spectrometry. ASP7991 was rapidly absorbed, metabolized and excreted...
March 7, 2018: Drug Metabolism and Pharmacokinetics
Caroline Gorvin
The calcium-sensing receptor (CaSR) is a class C G-protein coupled receptor (GPCR) that detects extracellular calcium concentrations, and modulates parathyroid hormone secretion and urinary calcium excretion to maintain calcium homeostasis. The CaSR utilises multiple heterotrimeric G-proteins to mediate signalling effects including: activation of intracellular calcium release; mitogen-activated protein kinase (MAPK) pathways; membrane ruffling; and inhibition of cAMP production. By studying germline mutations in the CaSR and proteins within its signalling pathway that cause hyper- and hypocalcaemic disorders, novel mechanisms governing GPCR signalling and trafficking have been elucidated...
March 29, 2018: Journal of Molecular Endocrinology
David Goltzman, Michael Mannstadt, Claudio Marcocci
Classic endocrine feedback loops ensure the regulation of blood calcium. Calcium in the extracellular fluid (ECF) binds and activates the calcium sensing receptor (CaSR) on the parathyroid cells, leading to an increase in intracellular calcium. This in turn leads to a reduced parathyroid hormone (PTH) release. Hypocalcemia leads to the opposite sequence of events, namely, lowered intracellular calcium and increased PTH production and secretion. PTH rapidly increases renal calcium reabsorption and, over hours to days, enhances osteoclastic bone resorption and liberates both calcium and phosphate from the skeleton...
2018: Frontiers of Hormone Research
Gozde Sengul Aycicek, Berna Imge Aydogan, Mustafa Sahin, Cevriye Cansız Ersoz, Serpil Dizbay Sak, Nilgun Baskal
We aimed to investigate the expressions of p27 kinase inhibitory protein 1 (p27Kip1 ) and calcium sensing receptor (CaSR) in adenomas and normal parathyroid tissue and to evaluate the relationship of these molecules with clinical and biochemical parameters in primary hyperparathyroidism (PHPT). Fifty-one patients with histopathologically confirmed parathyroid adenomas and 20 patients with normal parathyroid glands (which were removed incidentally during thyroid resection) were included. Immunohistochemical stainings of CaSR and p27Kip1 were performed in surgical specimens...
March 27, 2018: Endocrine Pathology
Andrea Gerbino, Matilde Colella
The current interest of the scientific community for research in the field of calcium sensing in general and on the calcium-sensing Receptor (CaR) in particular is demonstrated by the still increasing number of papers published on this topic. The extracellular calcium-sensing receptor is the best-known G-protein-coupled receptor (GPCR) able to sense external Ca2+ changes. Widely recognized as a fundamental player in systemic Ca2+ homeostasis, the CaR is ubiquitously expressed in the human body where it activates multiple signalling pathways...
March 27, 2018: International Journal of Molecular Sciences
Li Song, Li-Na Gao, Jun Wang, Swosti Thapa, Yong Li, Xiao-Bo Zhong, Hong-Wei Zhao, Xue-Rong Xiang, Fu-Gui Zhang, Ping Ji
Surgical flaps are frequently affected by ischemia/reperfusion (I/R) injury. Calcium-sensing receptor (CaSR) and stromal cell-derived factor-1 α (SDF-1 α ) are closely associated with myocardial I/R injury. This study was performed to evaluate the feasibility of applying SDF-1 α to counteract CaSR activation-mediated I/R injury in ischemic free flaps. Free flaps that underwent ischemia for 3 h were equally randomized into five groups: CaCl2 , NPS2143 + CaCl2 , SDF-1 α + CaCl2 , AMD3100 + SDF-1 α + CaCl2 , and normal saline...
2018: BioMed Research International
Nuran Sungu, Hayriye Tatli Dogan, Aydan Kiliçarslan, Mehmet Kiliç, Sefika Polat, Mehmet Tokaç, Soner Akbaba, Ömer Parlak, Serdar Balci, Betül Ögüt, Bekir Çakir
Background: As histopathological findings of parathyroid carcinoma are not certain, the diagnosis of tumors with degenerative changes may be difficult. In these cases, immunohistochemical markers are beneficial. We aimed to research the acceptability of calcium-sensing receptor (CaSR), Galactin-3, Cyclin D1, and Ki-67 as helpful markers in parathyroid tumors in cases which are difficult to diagnose. Materials and Methods: Those cases who had been diagnosed with atypical parathyroid adenoma and parathyroid carcinoma between 2010 and 2015 were reevaluated...
January 2018: Indian Journal of Pathology & Microbiology
Utkarsh Ojha
Obesity is a major global health issue. High-protein diets have been shown to be associated with weight loss and satiety. The precise mechanism by which protein-rich diets promote weight loss remains unclear. Evidence suggests amino acids, formed as a consequence of protein digestion, are sensed by specific receptors on L-cells in the gastrointestinal (GI) tract. These L-cells respond by secreting gut hormones that subsequently induce satiety. In recent years, the calcium-sensing receptor has been identified in several cells of the GI tract, including L-cells, and suggested to sense specific amino acids...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Andreas Kompatscher, J H F de Baaij, Karam Aboudehen, Shayan Farahani, Lex H J Van Son, Susanne Milatz, Nina Himmerkus, Gert Jan C Veenstra, René J M Bindels, Joost G J Hoenderop
Mutations in HNF1β cause autosomal dominant tubulointerstitial kidney disease (ADTKD-HNF1β), and patients tend to develop renal cysts, maturity-onset diabetes of the young (MODY), and suffer from electrolyte disturbances, including hypomagnesemia, hypokalemia and hypocalciuria. Previous HNF1β research focused on the renal distal convoluted tubule (DCT) to elucidate the ADTKD-HNF1β electrolyte phenotype, although 70% of Mg2+ is reabsorbed in the thick ascending limb of Henle's loop (TAL). An important regulator of Mg2+ reabsorption in the TAL is the calcium-sensing receptor (CaSR)...
March 21, 2018: American Journal of Physiology. Renal Physiology
Mohammad A BaSalamah, Abdelghany Hassan Abdelghany, Mohamed El-Boshy, Jawwad Ahmad, Shakir Idris, Bassem Refaat
This study measured the effects of vitamin D (VD) supplementation on the underlying molecular pathways involved in renal and testicular damage induced by lead (Pb) toxicity. Thirty two adult male Wistar rats were divided equally into four groups that were treated individually or simultaneously, except the negative control, for four weeks with lead acetate in drinking water (1,000 mg/L) and/or intramuscular VD (1,000 IU/kg; 3 days/week). Pb toxicity markedly reduced serum VD and Ca2+ , induced substantial renal and testicular injuries with concomitant significant alterations in the expression of VD metabolising enzymes, its receptor and binding protein, and the calcium sensing receptor...
March 19, 2018: Scientific Reports
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