CaSR

The Calcium-sensing receptor (CaSR) senses extracellular calcium, regulates parathyroid hormone (PTH) secretion, and has additional functions in various organs related to systemic and local calcium and mineral homeostasis. Familial hypocalciuric hypercalcemia type I (FHH1) is caused by heterozygous loss-of-function mutations in the CaSR gene, and is characterized by the combination of hypercalcemia, hypocalciuria, normal to elevated PTH, and facultatively hypermagnesemia and mild bone mineralization defects...

PURPOSE: Calcium-sensing receptor (CASR) influences the expression pattern of multiple genes in renal tubular epithelial cells. The objective of this inquiry was to explore the molecular mechanisms of CASR in renal tubular epithelial cells and nephrolithiasis. METHODS: HK-2 cells were transfected with lentiviruses carrying either CASR (named CASR) or an empty vector negative control (named NC), as well as shRNA intended to target CASR (named shCASR) or its corresponding negative control (named shNC)...

High concentrations of urinary calcium counteract vasopressin action via the activation of the Calcium-Sensing Receptor (CaSR) expressed in the luminal membrane of the collecting duct cells, which impairs the trafficking of aquaporin-2 (AQP2). In line with these findings, we provide evidence that, with respect to wild-type mice, CaSR knock-in (KI) mice mimicking autosomal dominant hypocalcaemia, display a significant decrease in the total content of AQP2 associated with significantly higher levels of AQP2 phosphorylation at Ser261, a phosphorylation site involved in AQP2 degradation...

PCOS is a widespread disease that primarily caused in-pregnancy in pregnant-age women. Normoandrogen (NA) and Hyperandrogen (HA) PCOS are distinct subtypes of PCOS, while bio-markers and expression patterns for NA PCOS and HA PCOS have not been disclosed. We performed microarray analysis on granusola cells from NA PCOS, HA PCOS and normal tissue from 12 individuals. Afterwards, microarray data were processed and specific genes for NA PCOS and HA PCOS were identified. Further functional analysis selected IL6R and CD274 as new NA PCOS functional markers, and meanwhile selected CASR as new HA PCOS functional marker...

BACKGROUND: Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcaemia (FHH) are common causes of hypercalcaemia. Patients are mostly asymptomatic in the case of FHH and often so in the case of PHPT. In addition, biochemical parameters show considerable overlap, making differential diagnosis difficult. Genetic screening for inactivating variants in the calcium-sensing receptor ( CASR ) gene that are causative of FHH assists with the diagnosis since such variants are not generally associated with PHPT...

Yeast extract, a widely utilized natural substance in the food industry and biopharmaceutical field, holds significant potential for flavor enhancement. Kokumi peptides within yeast extracts were isolated through ultrafiltration and gel chromatography, followed by identification using liquid chromatography tandem mass spectrometry (LC-MS/MS). Two peptides, IQGFK and EDFFVR, were identified and synthesized using solid-phase methods based on molecular docking outcomes. Sensory evaluations and electronic tongue analyses conducted with chicken broth solutions revealed taste thresholds of 0...

INTRODUCTION: Premenstrual symptoms encompass a range of physical, emotional, and behavioral changes that cyclically occur before menstruation. Childhood abuse has been associated with subsequent mental health challenges, yet its relationship with exacerbating premenstrual symptoms remains an understudied area. Furthermore, suicidal ideation often emerges from traumatic backgrounds such as child abuse, creating another layer of complexity. Given the rising suicide rates in Lebanon, and the concurrent increase in reported child abuse cases, this research focuses on the role of suicidal ideation as a mediator between child abuse and premenstrual syndrome...

The calcium-sensing receptor (CaSR) is a family C G-protein-coupled receptor1 (GPCR) that has a central role in regulating systemic calcium homeostasis2,3 . Here we use cryo-electron microscopy and functional assays to investigate the activation of human CaSR embedded in lipid nanodiscs and its coupling to functional Gi versus Gq proteins in the presence and absence of the calcimimetic drug cinacalcet. High-resolution structures show that both Gi and Gq drive additional conformational changes in the activated CaSR dimer to stabilize a more extensive asymmetric interface of the seven-transmembrane domain (7TM) that involves key protein-lipid interactions...

Agaricus bisporus contains amino acids associated with thickness and full-mouthfeel, making it a potential candidate for salt substitutes and flavor enhancers in various food applications. Kokumi peptides were isolated from the enzymatic digest of Agaricus bisporus using ultrafiltration nanofiltration, gel chromatographic separation, and RP-HPLC, coupled with sensory evaluation. Subsequently, the peptides, EWVPVTK and EYPPLGR, were selected for solid-phase synthesis based on molecular docking. Sensory analysis, including thresholds, time intensity, and dose-configuration relationships, indicated that EWVPVTK and EYPPLGR exhibited odor thresholds of 0...

BACKGROUND: Enterotoxins produce diarrhea through direct epithelial action and indirectly by activating the enteric nervous system. Calcium-sensing receptor (CaSR) inhibits both actions. The latter has been well documented in vitro but not in vivo . The hypothesis to be tested was that activating CaSR inhibits diarrhea in vivo . AIM: To determine whether CaSR agonists ameliorate secretory diarrhea evoked by cholera toxin (CTX) in mice. METHODS: CTX was given orally to C57BL/6 mice to induce diarrhea...

Pulmonary hypertension (PH) is characterized by elevation of pulmonary arterial pressure and pulmonary vascular resistance. The increased pulmonary arterial pressure and pulmonary vascular resistance due to sustained pulmonary vasoconstriction and pulmonary vascular remodeling can lead to right heart failure and eventual death. A rise in intracellular Ca2+ concentration ([Ca2+ ]i ) and enhanced pulmonary arterial smooth muscle cells (PASMCs) proliferation contribute to pulmonary vasoconstriction and pulmonary vascular remodeling...

Rainforest hunter-gatherers from South-East Asia are characterized by specific morphological features including a particularly dark skin color (D), short stature (S), woolly hair (W), and the presence of steatopygia (S) - fat accumulation localized in the hips (DSWS phenotype). Based on previous evidence in the Andamanese population, we first characterized signatures of adaptive natural selection around the Calcium-Sensing Receptor (CaSR) gene in SE Asian rainforest groups presenting the DSWS phenotype and identified the R990G substitution (rs1042636) as a putative adaptive variant for experimental follow-up...

Stimulation of the calcium-sensing receptor (CaSR) induces both vasoconstrictions and vasorelaxations but underlying cellular processes remain unclear. This study investigates expression and effect of stimulating the CaSR by increasing external Ca2+ concentration ([Ca2+ ]o ) on contractility of rat mesenteric arteries. Immunofluorescence studies showed expression of the CaSR in perivascular nerves, vascular smooth muscle cells (VSMCs), and vascular endothelium cells. Using wire myography, increasing [Ca2+ ]o from 1 to 10 mM induced vasorelaxations which were inhibited by the calcilytic Calhex-231 and partially dependent on a functional endothelium...

Transforming macrophages into the anti-inflammatory M2 phenotype could markedly strengthen inflammatory bowel disease (IBD) treatment, which is considered as a promising strategy. However, the high ferroptosis sensitivity of M2 macrophages, which decreases their activity, is a major stumbling block to this strategy. Therefore, promoting M2 polarization while simultaneously inhibiting ferroptosis to tackle this challenge is indispensable. Herein, a calcium‑carbonate (CaCO3 ) mineralized liposome encapsulating a ferroptosis inhibitor (Fer-1) was developed (CaCO3 @Lipo@Fer-1, CLF)...

When the skin is damaged, accelerating the repair of skin trauma and promoting the recovery of tissue function are crucial considerations in clinical treatment. Previously, we isolated and identified an active peptide (livisin) from the skin secretion of the frog Odorrana livida . Livisin exhibited strong protease inhibitory activity, water solubility, and stability, yet its wound-healing properties have not yet been studied. In this study, we assessed the impact of livisin on wound healing and investigated the underlying mechanism contributing to its effect...

Drugs acting as positive allosteric modulators (PAMs) to enhance the activation of the calcium sensing receptor (CaSR) and to suppress parathyroid hormone (PTH) secretion can treat hyperparathyroidism but suffer from side effects including hypocalcemia and arrhythmias. Seeking new CaSR modulators, we docked libraries of 2.7 million and 1.2 billion molecules against transforming pockets in the active-state receptor dimer structure. Consistent with the idea that docking improves with library size, billion-molecule docking found new PAMs with a hit rate that was 2...

OBJECTIVE: Biochemical suspicion of familial hypocalciuric hypercalcemia (FHH) might provide with a negative (FHH-negative) or positive (FHH-positive) genetic result. Understanding the differences between both groups may refine the identification of those with a positive genetic evaluation, aid management decisions and prospective surveillance. We aimed to compare FHH-positive and FHH-negative patients, and to identify predictive variables for FHH-positive cases. DESIGN: Retrospective, national multi-centre study of patients with suspected FHH and genetic testing of the CASR, AP2S1 and GNA11 genes...

Calcium is a ubiquitous second messenger that is indispensable in regulating neurotransmission and memory formation. A precise intracellular calcium level is achieved through the concerted action of calcium channels, and calcium exerts its effect by binding to an array of calcium-binding proteins, including calmodulin (CAM), calcium-calmodulin complex-dependent protein kinase-II (CAMK-II), calbindin (CAL), and calcineurin (CAN). Calbindin orchestrates a plethora of signaling events that regulate synaptic transmission and depolarizing signals...

BACKGROUND: Growing evidence points to an association between the gut microbiota and neonatal diseases. Calcium-sensing receptor (CaSR) is a major modulator of tissue responses associated with calcium homeostasis and is highly expressed in the mammalian gut. CaSR may affect the composition and balance of the intestinal microenvironment. METHODS: Neonatal rats were randomized to the control, lipopolysaccharide (LPS), CaSR agonist, and CaSR inhibitor groups. The intestinal contents of neonatal rats were collected within 24 hours or 7 days after intervention...

Cardiovascular disorders are commonly prevalent in cancer patients, yet the mechanistic link between them remains poorly understood. Because neutrophil extracellular traps (NETs) have implications not just in cardiovascular diseases (CVD), but also in breast cancer (BC), it was hypothesized to contribute to CVD in the context of oncogenesis. We established a mouse model using nude mice to simulate liver metastasis of triple-negative BC (TNBC) through the injection of MDA-MB-231 cells. Multiple imaging and analysis techniques were employed to assess the cardiac function and structure, including echocardiography, HE staining, Masson staining, and transmission electron microscopy (TEM)...