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https://www.readbyqxmd.com/read/29782837/phenylalanine-and-tryptophan-stimulate-gastrin-and-somatostatin-secretion-and-h-k-atpase-activity-in-pigs-through-calcium-sensing-receptor
#1
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
https://www.readbyqxmd.com/read/29777154/calcimimetic-acts-on-enteric-neuronal-casr-to-reverse-cholera-toxin-induced-intestinal-electrolyte-secretion
#2
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
https://www.readbyqxmd.com/read/29763933/the-calcium-sensing-receptor-gene-polymorphism-rs1801725-and-calcium-related-phenotypes-in-hemodialysis-patients
#3
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
https://www.readbyqxmd.com/read/29743878/identification-and-functional-characterization-of-a-novel-mutation-in-the-human-calcium-sensing-receptor-that-co-segregates-with-autosomal-dominant-hypocalcemia
#4
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
https://www.readbyqxmd.com/read/29724589/discovery-of-evocalcet-a-next-generation-calcium-sensing-receptor-agonist-for-the-treatment-of-hyperparathyroidism
#5
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
https://www.readbyqxmd.com/read/29714810/divergent-effects-of-strontium-and-calcium-sensing-receptor-positive-allosteric-modulators-calcimimetics-on-human-osteoclast-activity
#6
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
https://www.readbyqxmd.com/read/29704936/associations-between-single-nucleotide-polymorphisms-in-the-calcium-sensing-receptor-and-chronic-kidney-disease-mineral-and-bone-disorder-in-cats
#7
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
https://www.readbyqxmd.com/read/29695932/quantitative-assessment-of-the-clinical-susceptibility-of-calcium-sensing-receptor-polymorphisms-in-cancer-patients
#8
Haohai Huang, Tao Li, Dan Liao, Zhu Zhu, Yong Dong
Background: Accumulating evidence has suggested a relationship between calcium-sensing receptor ( CASR ) polymorphisms and cancer risk in different types of cancer; however, the findings from epidemiologic studies have been conflicting. The purpose of this meta-analysis was to assess the clinical susceptibility of CASR polymorphisms in cancer patients. Materials and methods: This study systematically searched MEDLINE and EMBASE databases for eligible articles through March 2017...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29682741/calcium-sensing-receptor-gene-polymorphism-rs7652589-is-associated-with-calcium-nephrolithiasis-in-the-population-of-yi-nationality-in-southwestern-china
#9
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
https://www.readbyqxmd.com/read/29682569/functions-and-signaling-pathways-of-amino-acids-in-intestinal-inflammation
#10
REVIEW
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
https://www.readbyqxmd.com/read/29681477/a-forward-genetic-screen-in-zebrafish-identifies-the-g-protein-coupled-receptor-casr-as-a-modulator-of-sensorimotor-decision-making
#11
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
https://www.readbyqxmd.com/read/29673577/profiling-of-g-protein-coupled-receptors-in-vagal-afferents-reveals-novel-gut-to-brain-sensing-mechanisms
#12
Kristoffer L Egerod, Natalia Petersen, Pascal N Timshel, Jens C Rekling, Yibing Wang, Qinghua Liu, Thue W Schwartz, Laurent Gautron
OBJECTIVES: G protein-coupled receptors (GPCRs) act as transmembrane molecular sensors of neurotransmitters, hormones, nutrients, and metabolites. Because unmyelinated vagal afferents richly innervate the gastrointestinal mucosa, gut-derived molecules may directly modulate the activity of vagal afferents through GPCRs. However, the types of GPCRs expressed in vagal afferents are largely unknown. Here, we determined the expression profile of all GPCRs expressed in vagal afferents of the mouse, with a special emphasis on those innervating the gastrointestinal tract...
April 3, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29662310/in-vitro-vivo-drug-release-and-anti-diabetic-cardiomyopathy-properties-of-curcumin-pblg-peg-pblg-nanoparticles
#13
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
https://www.readbyqxmd.com/read/29660510/the-in-vivo-anti-fibrotic-function-of-calcium-sensitive-receptor-casr-modulating-poly-p-dioxanone-co-l-phenylalanine-prodrug
#14
Bing Wang, Aiping Wen, Chengmin Feng, Lijing Niu, Xin Xiao, Le Luo, Chengyi Shen, Jiang Zhu, Jun Lei, Xiaoming Zhang
In present study, the apoptosis induction and proliferation suppression effects of l-phenylalanine (l-Phe) on fibroblasts were confirmed. The action sites of l-Phe on fibroblasts suppression were deduced to be calcium sensitive receptor (CaSR) which could cause the release of endoplasmic reticulum (ER) Ca2+ stores; disruption of intracellular Ca2+ homeostasis triggers cell apoptosis via the ER or mitochondrial pathways. The down-regulation of CaSR were observed after the application of l-Phe, and the results those l-Phe triggered the increasing of intracellular Ca2+ concentration and calcineurin expression, and then the apoptosis and increasing G1 fraction of fibroblasts have verified our deduction...
April 13, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29659895/identification-of-differential-transcriptional-patterns-in-primary-and-secondary-hyperparathyroidism
#15
Samira M Sadowski, Marc Pusztaszeri, Marie-Claude Brulhart-Meynet, Volodymyr Petrenko, Claudio De Vito, Jonathan Sobel, Céline Delucinge-Vivier, Electron Kebebew, Romano Regazzi, Jacques Philippe, Frédéric Triponez, Charna Dibner
Context: Hyperparathyroidism is associated with hypercalcemia and the excess of parathyroid hormone secretion. However, the alterations in molecular pattern of functional genes during parathyroid tumorigenesis have not been unraveled. We aimed at establishing transcriptional patterns of normal and pathological parathyroid glands (PG) in sporadic primary and secondary hyperparathyroidism (HPT1, 2). Objective: To evaluate dynamic alterations in molecular patterns as a function of the type of PG pathology, a comparative transcript analysis was conducted in subgroups of healthy samples, sporadic HPT1 adenoma and hyperplasia, and HPT2...
April 5, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29644008/calcium-sensing-receptor-casr-promotes-development-of-bone-metastasis-in-renal-cell-carcinoma
#16
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
https://www.readbyqxmd.com/read/29618612/interrelated-role-of-klotho-and-calcium-sensing-receptor-in-parathyroid-hormone-synthesis-and-parathyroid-hyperplasia
#17
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
https://www.readbyqxmd.com/read/29617866/serotonin-induces-parathyroid-hormone-related-protein-in-goat-mammary-gland
#18
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
https://www.readbyqxmd.com/read/29617283/regulation-of-bicarbonate-secretion-in-marine-fish-intestine-by-the-calcium-sensing-receptor
#19
Sílvia F Gregório, Juan Fuentes
In marine fish, high epithelial intestinal HCO₃&minus; 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&minus; 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
https://www.readbyqxmd.com/read/29599414/insights-into-calcium-sensing-receptor-trafficking-and-biased-signalling-by-studies-of-calcium-homeostasis
#20
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
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