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"Calcium sensing receptor"

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https://www.readbyqxmd.com/read/28431775/cinacalcet-hydrochloride
#1
Gamal A E Mostafa, Abdullah A Al-Badr
Cinacalcet hydrochloride is a calcimimetic agent that increases the sensitivity to the extracellular calcium of the calcium-sensing receptors of the parathyroid gland which regulates parathyroid hormone secretion. This comprehensive profile on cinacalcet hydrochloride starts with a description: nomenclature, formulae, chemical structure, elemental composition, and appearance. The uses and applications of the drug are included. The methods of preparation of cinacalcet hydrochloride are described and their respective schemes are outlined...
2017: Profiles of Drug Substances, Excipients, and related Methodology
https://www.readbyqxmd.com/read/28422826/idiopathic-hypoparathyroidism-with-extensive-intracranial-calcification-in-children-first-report-from-saudi-arabia
#2
Naglaa M Kamal, Hamed A Alghamdi, Abdulrahman A Halabi, Ayman A Bakkar, Ali Algarni, Abdullah Alharbi, Abdulla A Alharthi, Rawan A Alharbi, Laila M Sherief
RATIONALE: Pediatric idiopathic hypoparathyroidism with extensive intracranial calcifications outside the basal ganglia (BG) is extremely rare with less than 10 cases worldwide. PATIENT CONCERNS: An 11-year-old Saudi male child presented with tetany with otherwise normal neurological and other body system examination diagnoses severe hypocalcemia for differential diagnosis. INTERVENTIONS: Further investigations revealed hyperphosphatemia and undetectable serum intact parathyroid hormone...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28419469/the-endoplasmic-reticulum-associated-protein-os-9-behaves-as-a-lectin-in-targeting-the-immature-calcium-sensing-receptor
#3
Bryan K Ward, Sarah L Rea, Aaron L Magno, Bernadette Pedersen, Suzanne J Brown, Shelby Mullin, Ajanthy Arulpragasam, Evan Ingley, Arthur D Conigrave, Thomas Ratajczak
The mechanisms responsible for the processing and quality control of the calcium-sensing receptor (CaSR) in the endoplasmic reticulum (ER) are largely unknown. In a yeast two-hybrid screen of the CaSR C-terminal tail (residues 865 -1078), we identified osteosarcoma-9 (OS-9) protein as a binding partner. OS-9 is an ER-resident lectin that targets misfolded glycoproteins to the ER-associated degradation (ERAD) pathway through recognition of specific N-glycans by its mannose-6-phosphate receptor homology (MRH) domain...
April 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28417952/investigating-the-molecular-mechanism-of-positive-and-negative-allosteric-modulators-in-the-calcium-sensing-receptor-dimer
#4
Stine Engesgaard Jacobsen, Ulrik Gether, Hans Bräuner-Osborne
Allosteric modulators that are targeting the calcium-sensing receptor (CaSR) hold great therapeutic potential, and elucidating the molecular basis for modulation would thus benefit the development of novel therapeutics. In the present study, we aimed at investigating the mechanism of allosteric modulation in CaSR by testing dimers carrying mutations in the allosteric site of one or both of the subunits. To ensure measurements on a well-defined dimer composition, we applied a trans-activation system in which only the specific heterodimer of two loss-of-function mutants responded to agonist...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28368538/combined-deletion-of-the-vitamin-d-receptor-and-calcium-sensing-receptor-delays-wound-re-epithelialization
#5
Yuko Oda, Lizhi Hu, Thai Nguyen, Chak Fong, Chia-Ling Tu, Daniel D Bikle
When the skin is injured, keratinocytes proliferate, migrate, and differentiate to regenerate the epidermis. We recently showed that ablation of the vitamin D receptor (Vdr) in keratinocytes delays wound re-epithelialization in mice also fed a low calcium diet, implicating a cooperative role of Vdr and calcium signaling in this process. In this study we examined the role of vitamin D and calcium signaling in wound healing by deleting their receptors, Vdr and the calcium sensing receptor (Casr). Gene expression profiling of neonatal epidermis lacking both Vdr and Casr (DKO) specifically in keratinocytes revealed that DKO affects a number of pathways relevant to wound healing including Vdr, β-catenin and adherens junction signaling...
March 22, 2017: Endocrinology
https://www.readbyqxmd.com/read/28348014/hypoxia-induced-mitogenic-factor-acts-as-a-nonclassical-ligand-of-calcium-sensing-receptor-therapeutically-exploitable-for-intermittent-hypoxia-induced-pulmonary-hypertension
#6
Xianqin Zeng, Liping Zhu, Rui Xiao, Bingxun Liu, Mengxiang Sun, Fangbo Liu, Qiang Hao, Yankai Lu, Jiwei Zhang, Jiansha Li, Tao Wang, Xiang Wei, Qinghua Hu
Hypoxia-induced mitogenic factor (HIMF) is an inflammatory cytokine playing important role(s) in the development of hypoxic pulmonary hypertension. The molecular target mediating HIMF-stimulated downstream events remains unclear. The coimmunoprecipitation screen identified extracellular calcium-sensing receptor (CaSR) as the binding partner for HIMF in pulmonary artery smooth muscle cells. The yeast 2-hybrid assay then revealed the binding of HIMF to the intracellular, not the extracellular, domain of extracellular CaSR...
March 27, 2017: Hypertension
https://www.readbyqxmd.com/read/28336833/-oral-calcimimetics-on-secondary-hyperparathyroidism-of-uremia
#7
Yasuo Imanishi
Secondary hyperparathyroidism of uremia is associated with poor health outcomes, including all-cause mortality, cardiovascular mortality, and fractures. Standard therapy for secondary hyperparathyroidism includes vitamin D receptor activators, and phosphate binders. Persistently elevated parathyroid hormone(PTH)levels may require the addition of calcimimetics which sensitizes calcium-sensing receptors on the parathyroid glands.
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336831/-calcilytic-drugs-feature-and-future
#8
Itsuro Endo
Calcium-sensing receptor(CaSR)is highly expressed in parathyroid, kidney, bone, and small and large intestines to regulate Ca homeostasis. Calcilytics are allosteric antagonists of CaSR, and stimulate endogenous PTH release. Several calcilytics have been evaluated as anabolic therapies for postmenopausal osteoporosis but clinical development of all of them has been abandoned because the lacked clinical efficacy. Calcilytics might be repurposed for new indications like autosomal dominant hypocalcemia or other disorders...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336830/-the-discovery-research-and-development-of-etelcalcetide-hydrochloride-the-world-1st-intravenous-calcimimetics
#9
Atsuto Inoue, Kazutsune Harada
Etelcalcetide hydrochloride is the first intravenous calcimimetics agent for secondary hyperparathyroidism (SHPT). Etelcalcetide hydrochloride is to be administered through dialysis circuit by physician or medical staff upon completion of dialysis and such administration is expected to reduce the burden of medication in patients. From the nonclinical study results, etelcalcetide functions as an allosteric activator of calcium-sensing receptor(CaSR). Etelcalcetide suppressed PTH secretion both in vitro and in vivo...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336828/-disorders-caused-by-mutations-in-calcium-sensing-receptor-and-related-diseases
#10
Toshimi Michigami
Sensing of extracellular calcium(Ca2+)levels involves the Ca-sensing receptor(CaSR), its downstream signaling molecule Gα11, and the adaptor-related protein complex 2(AP2)that plays a role in clathrin-dependent endocytosis of CaSR. Inactivating mutations in CaSR cause familial hypocalciuric hypercalcemia type 1(FHH1)and neonatal severe hyperparathyroidism(NSHPT), while activating mutations lead to autosomal dominant hypocalcemia type 1(ADH1)and Bartter syndrome type Ⅴ. Recent studies have identified that inactivating mutations in Gα11 and σ-subunit of AP2(AP2σ)also cause FHH, and these conditions have been classified as FHH2 and FHH3, respectively...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336826/-etiology-and-pathogenesis-of-primary-hyperparathyroidism
#11
Mika Yamauchi, Toshitsugu Sugimoto
Primary hyperparathyroidism(pHPT)is a frequent endocrine disease in which abnormal calcium(Ca)regulation leads to hypercalcemia. The most frequent cause of pHPT in more than 80% of patients is an adenoma, followed by hyperplasia in about 15%, and cancer in 1~5%. Although most cases of pHPT are sporadic, a few are familial(hereditary), and this is known as familial hyperparathyroidism(FHPT). Gene abnormalities that affect cyclin D1 signaling(CCND1, CDC73, CDKN1B), Wnt/β-catenin signaling(MEN1), and calcium-sensing receptor signaling(CaSR, GNA11, AP2S1)play a role in the etiology and pathogenesis of pHPT...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336825/-divergent-functions-of-the-calcium-sensing-receptor-other-than-regulation-ofmineral-metabolism
#12
Daisuke Inoue
The calcium-sensing receptor(CaSR)is a G protein-coupled membrane receptor that binds extracellular Ca2+and other cations as a ligand. CaSR is expressed in parathyroid glands at the highest level and plays a critical role in the regulation of extracellular calcium. CaSR is also expressed by a wide variety of tissues other than calcium metabolic organs. In this overview, divergent roles of CaSR in inflammasome as well as various tissues including intestines, lungs, neurons and endocrine pancreas will be briefly summarized...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336824/-the-functions-of-calcium-sensing-receptor-in-regulating-mineral-metabolism
#13
Yuka Kinoshita
Calcium-sensing receptor(CaSR)which belongs to a G protein-coupled receptor family is one of the key elements in regulating calcium homeostasis. CaSR has been identified as a receptor to control parathyroid hormone(PTH)secretion in parathyroid glands according to serum calcium ion(Ca2+)levels. It has also been shown that CaSR controls reabsorption of water and several cations including Ca2+and magnesium ion(Mg2+)in renal tubular cells. This review summarizes the functions and roles of CaSR in mineral metabolism that are exerted in parathyroid glands, kidney, and intestine...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336431/calcium-sensing-receptor-antagonist-nps2390-attenuates-neuronal-apoptosis-though-intrinsic-pathway-following-traumatic-brain-injury-in-rats
#14
Zhaoliang Xue, Zhengfei Song, Yingfeng Wan, Kun Wang, Lianjie Mo, Yirong Wang
Traumatic brain injury (TBI) initiates a complex cascade of neurochemical and signaling changes that leads to neuronal apoptosis, which contributes to poor outcomes for patients with TBI. Previous study indicates that calcium-sensing receptor (CaSR) activation contributes to neuron death in focal cerebral ischemia-reperfusion mice, however, its role in neuronal apoptosis after TBI is not well-established. Using a controlled cortical impact model in rats, the present study was designed to determine the effect of CaSR inhibitor NPS2390 upon neuronal apoptosis after TBI...
March 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28330842/monocrotaline-induces-endothelial-injury-and-pulmonary-hypertension-by-targeting-the-extracellular-calcium-sensing-receptor
#15
Rui Xiao, Yuan Su, Tian Feng, Mengxiang Sun, Bingxun Liu, Jiwei Zhang, Yankai Lu, Jiansha Li, Tao Wang, Liping Zhu, Qinghua Hu
BACKGROUND: Monocrotaline has been widely used to establish an animal model of pulmonary hypertension. The molecular target underlying monocrotaline-induced pulmonary artery endothelial injury and pulmonary hypertension remains unknown. The extracellular calcium-sensing receptor (CaSR) and particularly its extracellular domain hold the potential structural basis for monocrotaline to bind. This study aimed to reveal whether monocrotaline induces pulmonary hypertension by targeting the CaSR...
March 22, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28323996/molecular-physiology-of-the-hypocalcemic-action-of-fibroblast-growth-factor-23-in-zebrafish-danio-rerio
#16
Chia-Hao Lin, Huei-Jyun Hu, Pung-Pung Hwang
Fibroblast growth factor 23 (FGF23), a hormone required for phosphorus metabolism, was recently proposed to act on Ca2+ uptake; however, the available evidences of how FGF23 controls the body fluid Ca2+ homeostasis needs to be further clarified. The use of zebrafish as a model system revealed that FGF23 is specifically expressed in the corpuscles of Stannius (CS), an organ involved in Ca2+ homeostasis in fish, and its expression is stimulated by ambient water with a high Ca2+ level. The overexpression of FGF23 inhibited Ca2+ uptake by downregulating the mRNA expression of epithelium calcium channel (ECaC)...
March 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28284837/casr-and-calpain-contribute-to-the-ischemia-reperfusion-injury-of-spinal-cord
#17
Ji-Fu Sun, Hui-Lin Yang, Yong-Hui Huang, Qian Chen, Xing-Bing Cao, Da-Peng Li, Hao-Ming Shu, Run-Yu Jiang
Spinal cord ischemia reperfusion injury (SCIRI) can cause spinal cord dysfunction and even devastating paraplegia. Calcium-sensing receptor (CaSR) and calpain are two calcium related molecules which have been reported to be involved in the ischemia reperfusion injury of cardiomyocytes and the subsequent apoptosis. Here, we studied the expression of CaSR and calpain in spinal cord neurons and tissues, followed by the further investigation of the role of CaSR/calpain axis in the cellular apoptosis process during SCIRI...
March 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28284102/g-protein-coupled-calcium-sensing-receptor-is-a-crucial-mediator-of-mta-induced-biological-activities
#18
Jin Man Kim, Seulki Choi, Kyu Hwan Kwack, Sun-Young Kim, Hyeon-Woo Lee, Kyungpyo Park
Mineral trioxide aggregate (MTA) is a calcium silicate-based bioactive material that has been extensively used in dentistry. MTA has been highlighted in its diverse biological functions and excellent clinical outcomes. However, limited insight into the intracellular signaling pathways has been provided to explain the biological activities of MTA. Here, we firstly elucidate that the extracellular calcium-sensing receptor (CaSR) is a major signaling mediator of MTA-induced biological reactions through versatile live imaging techniques of human dental pulp cells (hDPCs)...
February 28, 2017: Biomaterials
https://www.readbyqxmd.com/read/28281186/calcium-sensing-receptor-mediated-mitogen-activated-protein-kinase-pathway-improves-the-status-of-transplanted-mouse-embryonic-stem-cells-in-rats-with-acute-myocardial-infarction
#19
Jian Sun, Tao Wei, Shuzhi Bai, Hongtao Zhao, Xiaoqin Liu, Jinfeng Yu, Li Li, Gaochen Song, Hairong Luan, Changqing Xu
Several studies have identified the critical role of calcium-sensing receptors (CaSRs) in cardiac ischaemia/reperfusion injury and cardiac hypertrophy and have demonstrated that CaSRs induce myocardial apoptosis by activating MAPKs. Using acute myocardial infarction rat models, we found that a combination therapy of CaSR inhibition and embryonic stem cell (ESC) transplantation after acute myocardial infarction (AMI) leads to a dramatic reduction in the infarct size; a significant increase in the maximum rising and falling rate (+dp/dtmax and -dp/dtmax, respectively) of left ventricular pressure; a significant decrease in left ventricular end-diastolic pressure; a significant decrease in the mRNA expression level of CaSR, Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, p-ERK, p-JNK and p-P38 protein together with apoptosis indexes in the C and E groups; and a significant decrease in cTnT levels as well as LDH and CK activity...
March 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28277829/etelcalcetide-for-the-treatment-of-secondary-hyperparathyroidism
#20
REVIEW
Naoto Hamano, Hirotaka Komaba, Masafumi Fukagawa
Calcium sensing receptor is an important target for the treatment of secondary hyperparathyroidism (SHPT). Etelcalcetide hydrochloride is a novel peptide calcimimetic agent that has a similar mechanism of action as cinacalcet hydrochloride. Clinical trials of etelcalcetide have been performed in the US, Europe, and Japan, and these trials demonstrated the safety and efficacy of etelcalcetide in dialysis patients. Etelcalcetide has recently been approved in Europe, the US and Japan. Areas covered: We review the development, pharmacokinetics, and clinical efficacy and safety of etelcalcetide for the treatment of SHPT in hemodialysis patients...
April 2017: Expert Opinion on Pharmacotherapy
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