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Calcium Sensing Receptor

Natalia Di Pietro, Maria Assunta Potenza, Sara Di Silvestre, Francesco Addabbo, Nadia Di Pietrantonio, Pamela Di Tomo, Caterina Pipino, Domitilla Mandatori, Carola Palmerini, Paola Failli, Mario Bonomini, Monica Montagnani, Assunta Pandolfi
The potential role of calcimimetics as vasculotropic agents has been suggested since the discovery that calcium sensing receptors (CaSRs) are expressed in cardiovascular tissues. However, whether this effect is CaSR-dependent or -independent is still unclear. In the present study the vascular activity of calcimimetic R-568 was investigated in mesenteric vascular beds (MVBs) isolated from Spontaneously Hypertensive rats (SHR) and the relative age-matched Wistar-Kyoto (WKY) control rats. Pre-constricted MBVs were perfused with increasing concentrations of R-568 (10 nM- 30 μM) resulting in a rapid dose-dependent vasodilatation...
2018: PloS One
Chao Wang, Cuicui Kang, Yihan Xian, Mingyu Zhang, Xiaolin Chen, Mingcai Pei, Weiyun Zhu, Suqin Hang
Nutrients regulate the secretion of gut satiety hormones, which is related to the modulation of food intake and blood glucose levels. Calcium-sensing receptor (CaSR) is involved in regulating gut hormone secretion in response to l-amino acids and multivalent cations. Rodents are often used to investigate the effect of nutrients on these hormonal release. However, results obtained using rodent models are difficult to be applied in humans, we used pigs as a model in this study because their physiology is similar to that of humans...
August 8, 2018: Journal of Food Science
Anna Jovanovich, Jessica Kendrick
Chronic kidney disease mineral bone disorder (CKD-MBD) is common in end-stage renal disease and is associated with an increased risk of cardiovascular morbidity and mortality. Mainstays of treatment include decreasing serum phosphorus level toward the normal range with dietary interventions and phosphate binders and treating increased parathyroid hormone levels with activated vitamin D and/or calcimimetics. There is significant variation in serum levels of mineral metabolism markers, intestinal absorption of phosphorus, and therapeutic response among individual patients and subgroups of patients with end-stage renal disease...
July 2018: Seminars in Nephrology
Gordon L Klein
The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and magnesium by bone resorption may sustain and intensify the inflammatory response. We used a burn injury setting in humans and a burn injury model in animals in order to examine the effects on the bone of the systemic inflammatory response and identified the parathyroid calcium-sensing receptor as the mediator of increasing bone resorption, hence higher interleukin (IL)-1 production, and decreasing bone resorption, hence the lowering of circulating ionized calcium concentration...
August 1, 2018: Biomolecules
Tina Pangrsic, Joshua H Singer, Alexandra Koschak
Calcium influx through voltage-gated Ca (CaV ) channels is the first step in synaptic transmission. This review concerns CaV channels at ribbon synapses in primary sense organs and their specialization for efficient coding of stimuli in the physical environment. Specifically, we describe molecular, biochemical, and biophysical properties of the CaV channels in sensory receptor cells of the retina, cochlea, and vestibular apparatus, and we consider how such properties might change over the course of development and contribute to synaptic plasticity...
October 1, 2018: Physiological Reviews
Caroline M Gorvin, Morten Frost, Tomas Malinauskas, Treena Cranston, Hannah Boon, Christian Siebold, E Yvonne Jones, Fadil M Hannan, Rajesh V Thakker
The calcium-sensing receptor (CaSR) is a homodimeric G-protein coupled receptor that signals via intracellular calcium (Ca2+i) mobilisation and phosphorylation of extracellular signal-regulated kinase (ERK) to regulate extracellular calcium (Ca2+e) homeostasis. The central importance of the CaSR in Ca2+e homeostasis has been demonstrated by the identification of loss- or gain-of-function CaSR mutations that lead to familial hypocalciuric hypercalcaemia (FHH) or autosomal dominant hypocalcaemia (ADH), respectively...
July 20, 2018: Human Molecular Genetics
Shunsuke Goto
Calcimimetics are widely used for severe secondary hyperparathyroidism in hemodialysis patients. Two clinical studies showed that cinacalcet, one of calcimimetics, has possibility to reduce the risk of fracture in hemodialysis patients. Although the mechanism in which calcimimetics reduce the risk of fracture in hemodialysis patients remains unclear, improvement of severe secondary hyperparathyroidism may cause the reduction of fracture risk. However, the optimal intact PTH levels for reducing the risk of fracture in hemodialysis patients is not known...
2018: Clinical Calcium
Bo Yin, Xu-Wei Hou, Mei-Li Lu
Astragaloside IV (AsIV) is an active saponin extracted from Astragalus membranaceus, which has shown cardioprotective effects in a number of experimental animals. In this study we investigated the molecular mechanisms by which AsIV attenuated the myocardial ischemia reperfusion (MI/R)-induced injury in vitro and in vivo by focusing on calcium-sensing receptor (CaSR) and extracellular signal-regulated kinase 1/2 (ERK1/2). Rat neonatal cardiac myocytes were subjected to a hypoxia/reoxygenation (H/R) procedure in vitro, which significantly decreased the cell viability, increased lactate dehydrogenase (LDH) release, induced cardiomyocyte apoptosis, and increased [Ca2+ ]i ...
July 20, 2018: Acta Pharmacologica Sinica
Alexander V Maltsev
True hibernators are remarkable group of mammals whose hearts are resistant to such stressors as deep hypothermia, ischemia, arrhythmia. Capability of cardiac cells from hibernating species to effectively rule Ca2+ homeostasis during torpor is poorly studied. Better understanding of these mechanisms could allow to introduce new strategies for improvement the cardiac performance and may be useful for cardiovascular medicine. Here for the first time we have shown that the regulation of Ca2+ handling and thereby cardiomyocyte contractility by endogenous neurotransmitter agmatine occurs through the modulation of calcium-sensing receptor (CaSR)...
July 17, 2018: Cellular Signalling
Erick O Hernández-Ochoa, Martin F Schneider
The process by which muscle fiber electrical depolarization is linked to activation of muscle contraction is known as excitation-contraction coupling (ECC). Our understanding of ECC has increased enormously since the early scientific descriptions of the phenomenon of electrical activation of muscle contraction by Galvani that date back to the end of the eighteenth century. Major advances in electrical and optical measurements, including muscle fiber voltage clamp to reveal membrane electrical properties, in conjunction with the development of electron microscopy to unveil structural details provided an elegant view of ECC in skeletal muscle during the last century...
July 19, 2018: Skeletal Muscle
Yingsong Hao, Wenxing Yang, Jing Ren, Qi Hall, Yun Zhang, Joshua M Kaplan
Nitric oxide (NO) is released into the air by NO-producing organisms; however, it is unclear if animals utilize NO as a sensory cue. We show that C. elegans avoids Pseudomonas aeruginosa (PA14) in part by detecting PA14-produced NO. PA14 mutants deficient for NO production fail to elicit avoidance and NO donors repel worms. PA14 and NO avoidance are mediated by a chemosensory neuron (ASJ) and these responses require receptor guanylate cyclases and cyclic nucleotide gated ion channels. ASJ exhibits calcium increases at both the onset and removal of NO...
July 17, 2018: ELife
Keith E Eidman, James B Wetmore
Secondary hyperparathyroidism (SHPT), commonly encountered in patients receiving maintenance dialysis, is associated with numerous adverse outcomes, including mortality. Calcimimetics, agents that act on the calcium sensing receptor (CaSR), were designed to overcome limitations in the use of vitamin D sterols to treat SHPT, and have demonstrated efficacy in reducing levels of PTH in randomized trials. Currently available calcimimetics include oral cinacalcet and the recently approved intravenously administered agent, etelcalcetide...
July 15, 2018: Seminars in Dialysis
Taisuke Shimizu, Kaori Takayanagi, Takatsugu Iwashita, Akira Ikari, Naohiko Anzai, Shimpei Okazaki, Hiroaki Hara, Minoru Hatano, Tatsuro Sano, Tomonari Ogawa, Koichi Kanozawa, Hajime Hasegawa
Tubulo-interstitial nephropathy (TIN) is a critical pathological setting for the renal prognosis, and an increase in the urine magnesium excretion is a well-known characteristic feature as one of clinical parametets for the assessment of TIN. We examined the correlation between the development of TIN and the changes in the mRNA expression of renal magnesium-transporting molecules in rats with unilateral ureter obstruction (UUO). Ureter-ligated kidney was sampled at day-0 (control), day-1 (early phase) and day-7 (late phase)...
July 10, 2018: Magnesium Research: Official Organ of the International Society for the Development of Research on Magnesium
Jung-Eun Moon, Su-Jeong Lee, Suk-Hyun Park, Jinsup Kim, Dong-Kyu Jin, Cheol Woo Ko
Autosomal-dominant hypocalcemia with hypercalciuria (ADHH) is a genetic disease characterized by hypoparathyroidism with hypercalciuria. Most patients with ADHH have calcium-sensing receptor (CaSR) gene mutations. The CaSR gene controls parathyroid secretions, and mutations in this gene can be detected via changes in serum calcium level. The activating mutation of the CaSR gene results in familial or sporadic ADHH. Most activating mutations of the CaSR gene are reportedly de novo missense mutations. This is the first case report of a novel activating variant of the CaSR gene in a neonate with congenital hypoparathyroidism with hypomagnesemia and hypercalciuria...
June 2018: Annals of Pediatric Endocrinology & Metabolism
Arunkumar Renganathan Chandrika, Mathew Steephan, Rajeevkumar Raveendran Nair, Suma Priya Sudarsana Devi, Mantosh Kumar, Soumya Paul, Mayadevi Madhavan, Ramakrishnapillai V Omkumar
Cellular calcium signaling events are transient. Hence they are observed in real time using fluorescence imaging or electrophysiological methods that require sophisticated instrumentation and specialized skills. For high throughput assays simple and inexpensive techniques are desirable. Many calcium channels that serve as drug targets have subtypes arising from diverse subunit combinations. These need to be targeted selectively for achieving efficacy and for avoiding side effects in therapies. This in turn increases the number of calcium channels that act as drug targets...
June 1, 2018: Cell Calcium
Beyza Goncu, Emrah Yucesan, Burcu Ozdemir, Harun Basoglu, Nur Ozten Kandas, Fahri Akbas, Erhan Aysan
BACKGROUND: Cold ischemia protects organs and tissues by slowing their metabolism, but it also causes ischemic injury. Minimizing cold ischemia has been an important goal in parathyroid auto- and allotransplantation, as well as the transplantation of other major organs. Parathyroid glands are responsible for calcium homeostasis by releasing parathormone (PTH) into the blood circulation. Functionality of a new parathyroid transport solution (NPTS) and effects on cell viability, PTH secretion, and calcium-sensing receptor (CaSR) levels during cold ischemia were evaluated...
July 2, 2018: Biopreservation and Biobanking
Priscilla Marys Costa Dos Santos, Deividi Amaral, Ana Lucia Tararthuch, Ricardo Fernandez
BACKGROUND: The calcium-sensing receptor (CaSR) is localized in the apical membrane of proximal tubules in close proximity to the transporters responsible for proton secretion. Therefore, the aim of the present study was to analyze the effects of CaSR stimulation on the biochemical activity of the vacuolar H+ -ATPase in a cellular model of proximal tubule cells, OKP cells. METHODS: Biochemical activity of H+ -ATPase was performed using cell homogenates, and the inorganic phosphate released was determined by a colorimetric method...
June 30, 2018: Clinical and Experimental Nephrology
Ping Zhou, Huai-Sha Xu, Meng-Meng Li, Xiao-Dong Chen, Jun Wang, Hua-Bin Zhou, Ling Chen, Ning Zhang, Na Liu
Predators induce defensive responses and fear behaviours in prey. The rat exposure test (RET) is frequently used as an animal model of panic. Nitric oxide (NO) which has been reported to be activated by the NMDA receptor, in turn mediates calcium/calmodulin-dependent protein kinase II (CaMKII) signalling pathways in defensive responses. ACCN2, the orthologous human gene of acid-sensing ion channel 1a (ASIC1a), is also associated with panic disorder; however, few studies have focused on the role of ASIC1a in the modulation of panic and calcium/CaMKII signalling by NO...
June 25, 2018: Behavioural Brain Research
Kelly J Culhane, Morgan E Belina, Jeremiah N Sims, Yingying Cai, Yuting Liu, Pam S P Wang, Elsa C Y Yan
Parathyroid hormone (PTH) binds to a family B G protein coupled receptor, parathyroid hormone 1 receptor (PTH1R). One of its functions is to regulate Ca2+ homeostasis in bone remodeling, during which Ca2+ can reach up to 40 mM. A truncated version of PTH, PTH(1-34), can fully activate PTH1R and has been used for osteoporosis treatments. Here, we used fluorescence anisotropy to examine the binding of PTH(1-34) to PTH1R purified in nanodiscs (PTH1R-ND) and found that the affinity increases 5-fold in the presence of 15 mM Ca2+ ...
July 11, 2018: ACS Chemical Biology
Hyesoo Youn, Colleen Kirkhart, Justine Chia, Kristin Scott
Octopamine regulates feeding behavioral responses in Drosophila melanogaster, however the molecular and circuit mechanisms have not been fully elucidated. Here, we investigated the role of a subset of octopaminergic neurons, the OA-VPM4 cluster, in sucrose acceptance behavior. Thermogenetic activation of Gal4 lines containing OA-VPM4 promoted proboscis extension to sucrose, while optogenetic inactivation reduced extension. Anatomically, the presynaptic terminals of OA-VPM4 are in close proximity to the axons of sugar-responsive gustatory sensory neurons...
2018: PloS One
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