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Calcium Sensing Receptor

Stephen J Marx, David Goltzman
We review advancing and overlapping stages for our understanding of the expressions of six hyperparathyroid (HPT) syndromes: multiple endocrine neoplasia type 1 (MEN1) or type 4, multiple endocrine neoplasia type 2A (MEN2A), hyperparathyroidism-jaw tumor syndrome, familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and familial isolated hyperparathyroidism. During stage 1 (1903 to 1967), the introduction of robust measurement of serum calcium was a milestone that uncovered hypercalcemia as the first sign of dysfunction in many HPT subjects, and inheritability was reported in each syndrome...
December 10, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Min Wu, Si-Si Wang, Jing-Yuan Cao, Tao-Tao Tang, Min Gao, Kun-Ling Ma, Bi-Cheng Liu
The mechanisms that underlie the profibrotic effect of interleukin (IL)-1β are complicated and not fully understood. Recent evidence has suggested the involvement of the calcium-sensing receptor (CaSR) in tubular injury. Therefore, the current study aimed to investigate whether CaSR mediates IL-1β-induced collagen expression in cultured mouse inner medullary collecting duct cells (mIMCD3) and to determine the possible downstream signaling effector. The results showed that IL-1β significantly upregulated the expression of type I and III collagens in a concentration- and time-dependent manner...
December 7, 2018: Journal of Cellular Biochemistry
Gioia Lenzoni, Marc R Knight
Plants need to sense increases in temperature to be able to adapt their physiology and development to survive; however, the mechanisms of heat perception are currently relatively poorly understood. Here we demonstrate that in response to elevated temperature the free calcium concentration of the stroma of chloroplasts increases. This response is specific to the chloroplast, as no corresponding increase in calcium is seen in the cytosol. The chloroplast calcium response is dose-dependent above a threshold. The magnitude of this calcium response is dependent upon absolute temperature, not rate of heating...
December 4, 2018: Plant & Cell Physiology
Monika Proszkowiec-Weglarz, Lori L Schreier, Katarzyna B Miska, Roselina Angel, Stanislaw Kahl, Beverly Russell
Calcium (Ca) and phosphorus (P) are essential minerals involved in many biological processes including bone development and mineralization. Plasma concentration of both minerals is tightly regulated, and Ca and P homeostasis is maintained via intestinal absorption, bone storage and exchange, and renal reabsorption. In the current broiler production systems, chicks are deprived of food and water for up to 72 h due to uneven hatching, hatchery procedures, and transportation time to farms. Post-hatch (PH) feed delay results in lower body and organ weight, higher feed conversion ratio and mortality, and delayed PH growth and GIT development...
December 3, 2018: Poultry Science
Mian Zhang, Hongxu Yang, Xianghong Wan, Lei Lu, Jing Zhang, Hongyun Zhang, Tao Ye, Qian Liu, Mianjiao Xie, Shibin Yu, Shaoxiong Guo, Wenhan Chang, Meiqing Wang
Traumatic joint injuries produce osteoarthritic cartilage manifesting accelerated chondrocyte terminal differentiation and matrix degradation via unknown cellular and molecular mechanisms. Here we report the ability of biomechanical stress to increase expression of the calcium-sensing receptor (CaSR), a pivotal driver of chondrocyte terminal differentiation, in cultured chondrogenic cells subjected to fluid flow shear stress (FFSS) and in chondrocytes of rodent temporomandibular joint (TMJ) cartilage subjected to unilateral anterior cross-bite (UAC)...
November 29, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Diana Ovejero, Barbara M Misof, Rachel I Gafni, David Dempster, Hua Zhou, Klaus Klaushofer, Michael T Collins, Paul Roschger
The role of the calcium-sensing receptor (CaSR) as a regulator of parathyroid hormone secretion is well established, but its function in bone is less well defined. In an effort to elucidate the CaSR's skeletal role, bone tissue and material characteristics from patients with autosomal dominant hypocalcemia (ADH), a genetic form of primary hypoparathyroidism caused by CASR gain-of-function mutations, were compared to patients with postsurgical hypoparathyroidism (PSH). Bone structure and formation/resorption indices and mineralization density distribution (BMDD), were examined in transiliac biopsy samples from PSH (n = 13) and ADH (n = 6) patients by histomorphometry and quantitative backscatter electron imaging, respectively...
November 29, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Helene H Jensen, Malene Brohus, Mette Nyegaard, Michael T Overgaard
Fluxes of calcium (Ca2+ ) across cell membranes enable fast cellular responses. Calmodulin (CaM) senses local changes in Ca2+ concentration and relays the information to numerous interaction partners. The critical role of accurate Ca2+ signaling on cellular function is underscored by the fact that there are three independent CaM genes ( CALM1-3 ) in the human genome. All three genes are functional and encode the exact same CaM protein. Moreover, CaM has a completely conserved amino acid sequence across all vertebrates...
2018: Frontiers in Molecular Neuroscience
You Chul Chung, Ji Hee Lim, Hyun Mi Oh, Hyung Wook Kim, Min Young Kim, Eun Nim Kim, Yaeni Kim, Yoon Sik Chang, Hye Won Kim, Cheol Whee Park
Decreased AMPK-eNOS bioavailability mediates the development of diabetic peripheral neuropathy (DPN) through increased apoptosis and decreased autophagy activity in relation to oxidative stress. Schwann cells are responsible for maintaining structural and functional integrity of neurons and for repairing damaged nerves. We evaluated the neuro-protective effect of cinacalcet on DPN by activating the AMPK-eNOS pathway using db/db mice and human Schwann cells (HSCs). Sciatic nerve of db/db mice was characterized by disorganized myelin, axonal shrinkage, and degeneration that were accompanied by marked fibrosis, inflammation, and apoptosis...
November 26, 2018: Cell Death & Disease
Alexander Panossian, Ean-Jeong Seo, Thomas Efferth
INTRODUCTION: Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. Adaptogens stimulate cellular and organismal defense systems by activating intracellular and extracellular signaling pathways and expression of stress-activated proteins and neuropeptides. The effects adaptogens on mediators of adaptive stress response and longevity signaling pathways have been reported, but their stress-protective mechanisms are still not fully understood...
November 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Palaniappan Sethu, Thomas A Haglund, Aaron J Rogers, Herbert Chen, John Porterfield, Courtney J Balentine
We developed a novel model for studying hyperparathyroidism by growing ex vivo 3-dimensional human parathyroids as part of a microphysiological system (MPS) that mimics human physiology. The purpose of this study was to validate the parathyroid portion of the MPS. We prospectively collected parathyroid tissue from 46 patients with hyperparathyroidism for growth into pseudoglands. We evaluated pseudogland architecture and calcium responsiveness. Following 2 weeks in culture, dispersed cells successfully coalesced into pseudoglands ∼500-700 µm in diameter that mimicked the appearance of normal parathyroid glands...
November 22, 2018: Cells, Tissues, Organs
Sule Terzioglu-Usak, Birsen Elibol, Tugce Dalli, Cansu Guler, Erhan Aysan
Background: There are limited numbers of experimental studies related to the potential role of parathormone/parathyroid hormone (PTH) in response to psychological stress. In the current study, we aimed to cross-examine, for the first time, changes in PTH plasma concentration and the expression of its molecular targets mediated by restraint stress in rats. Methods: Male Wistar rats (n = 42) were separated into control and stressed groups. They were further divided into two groups that received chronic restraint stress (CRS) for 7 and 28 consecutive days (n = 7 for each group)...
October 2018: International Journal of Endocrinology and Metabolism
Chuang Li, Fang Qin, Mengmeng Xue, Yucong Lei, Fen Hu, Hui Xu, Guihong Sun, Tao Wang, Mingxiong Guo
Cytosolic free Ca2+ concentration is a key factor in pulmonary vasoconstriction and vascular remodeling of pulmonary artery smooth muscle cells (PASMC). These processes contribute to pulmonary arterial hypertension and are influenced by expression of calcium sensing receptor (CaSR). Although regulation of CaSR expression is precisely controlled, the contribution of microRNAs is incompletely understood. Here, we demonstrate that miR-429, miR-424-5p, miR-200b-3p, and miR-200c-3p regulate CaSR by targeting specific 3'-UTR, suggesting that these miRNAs function as CaSR inhibitors in PASMC...
November 21, 2018: American Journal of Physiology. Cell Physiology
Pawin Pongkorpsakol, Chavin Buasakdi, Thanyatorn Chantivas, Varanuj Chatsudthipong, Chatchai Muanprasat
Intestinal barrier function depends on integrity of tight junctions, which serve as barriers to transepithelial influx of noxious substances/microorganisms from gut lumen. The G-protein coupled receptor 39 (GPR39) is a zinc-sensing receptor, which is expressed in several cell types including intestinal epithelial cells (IECs). The main objective of this study was to investigate the effect of GPR39 activation on tight junction assembly in IECs. Treatment with TC-G 1008 (1 μM -10 μM), a GPR39 agonist, and zinc (10 μM -100 μM) increased tight junction assembly in T84 cells...
October 26, 2018: European Journal of Pharmacology
Martin Bitzan, Paul R Goodyer
Hypophosphatemic rickets, mostly of the X-linked dominant form caused by pathogenic variants of the PHEX gene, poses therapeutic challenges with consequences for growth and bone development and portends a high risk of fractions and poor bone healing, dental problems and nephrolithiasis/nephrocalcinosis. Conventional treatment consists of PO4 supplements and calcitriol requiring monitoring for treatment-emergent adverse effects. FGF23 measurement, where available, has implications for the differential diagnosis of hypophosphatemia syndromes and, potentially, treatment monitoring...
February 2019: Pediatric Clinics of North America
Janet Y Lee, Dolores M Shoback
Familial hypocalciuric hypercalcemia (FHH) causes hypercalcemia by three genetic mechanisms: inactivating mutations in the calcium-sensing receptor, the G-protein subunit α11 , or adaptor-related protein complex 2, sigma 1 subunit. While hypercalcemia in other conditions causes significant morbidity and mortality, FHH generally follows a benign course. Failure to diagnose FHH can result in unwarranted treatment or surgery for the mistaken diagnosis of primary hyperparathyroidism (PHPT), given the significant overlap of biochemical features...
October 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
Giuseppe Vezzoli, Lorenza Macrina, Giulia Magni, Teresa Arcidiacono
Calcium-sensing receptor (CaSR) is a plasma-membrane G protein-coupled receptor activated by extracellular calcium and expressed in kidney tubular cells. It inhibits calcium reabsorption in the ascending limb and distal convoluted tubule when stimulated by the increase of serum calcium levels; therefore, these tubular segments are enabled by CaSR to play a substantial role in the regulation of serum calcium levels. In addition, CaSR increases water and proton excretion in the collecting duct and promotes phosphate reabsorption and citrate excretion in the proximal tubule...
November 16, 2018: Urolithiasis
Fadil M Hannan, Enikö Kallay, Wenhan Chang, Maria Luisa Brandi, Rajesh V Thakker
The Ca2+ -sensing receptor (CaSR) is a dimeric family C G protein-coupled receptor that is expressed in calcitropic tissues such as the parathyroid glands and the kidneys and signals via G proteins and β-arrestin. The CaSR has a pivotal role in bone and mineral metabolism, as it regulates parathyroid hormone secretion, urinary Ca2+ excretion, skeletal development and lactation. The importance of the CaSR for these calcitropic processes is highlighted by loss-of-function and gain-of-function CaSR mutations that cause familial hypocalciuric hypercalcaemia and autosomal dominant hypocalcaemia, respectively, and also by the fact that alterations in parathyroid CaSR expression contribute to the pathogenesis of primary and secondary hyperparathyroidism...
November 15, 2018: Nature Reviews. Endocrinology
Masahide Mizobuchi, Hiroaki Ogata, Fumihiko Koiwa
The classic pathogenesis of secondary hyperparathyroidism (SHPT) began with the trade-off hypothesis based on parathyroid hormone (PTH) hypersecretion brought about by renal failure resulting from a physiological response to correct metabolic disorder of calcium, phosphorus, and vitamin D. In dialysis patients with failed renal function, physiological mineral balance control by PTH through the kidney fails and hyperparathyroidism progresses. In this process, many significant genetic findings have been established...
November 8, 2018: Therapeutic Apheresis and Dialysis
Alejandro García, Leire Madariaga, Gustavo Pérez de Nanclares, Gema Ariceta, Sonia Gaztambide, Spanish Endocrinology Group, Renaltube Group, Luis Castaño
OBJECTIVE: Molecular diagnosis is a useful diagnostic tool in calcium metabolism disorders. The calcium-sensing receptor (CaSR) is known to play a central role in the regulation of extracellular calcium homeostasis. We performed clinical, biochemical and genetic characterization of sequence anomalies in this receptor in a cohort of 130 individuals from 82 families with suspected alterations in the CASR gene, one of the largest series described. METHODS: The CASR gene was screened for mutations by polymerase chain reaction followed by direct Sanger sequencing...
November 1, 2018: European Journal of Endocrinology
Xiaomei Sun, Liang Huang, Jin Wu, Yuhong Tao, Fan Yang
RATIONALE: Calcium-sensing receptor (CaSR) mutations can cause life-threatening neonatal severe hyperparathyroidism (NSHPT). The medical management of NSHPT is often challenging and complex. Here, we present a case of NSHPT caused by a novel homozygous CaSR mutation. PATIENT CONCERNS: A Chinese female infant presented with poor feeding, constipation, severe hypotonia, and periodic bradycardia. Biochemistry tests revealed markedly elevated serum levels of Ca and parathyroid hormone (PTH)...
November 2018: Medicine (Baltimore)
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