scholarly journals A Ca2+-sensing receptor modulates shark rectal gland function

2002 ◽  
Vol 205 (13) ◽  
pp. 1889-1897 ◽  
Author(s):  
Susan K. Fellner ◽  
Laurel Parker
Keyword(s):  
Ionic Strength ◽  
Sea Water ◽  
Extracellular Fluid ◽  
Plasma Osmolality ◽  
Rectal Gland ◽  
Ip3 Receptors ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Gland Function ◽  
Salt Secretion

SUMMARY The elasmobranch Squalus acanthias controls plasma osmolality and extracellular fluid volume by secreting a hypertonic fluid from its rectal gland. Because we found a correlation between extracellular Ca2+concentration and changes in cytosolic Ca2+([Ca2+]i), we sought the possible presence of a calcium-sensing receptor in rectal gland artery and tubules. Cytosolic Ca2+ of both tissues responded to the addition of external Ca2+ (0.8-5.3 mmol l-1) in a linear fashion. Spermine,Gd3+ and Ni2+, known agonists of the calcium-sensing receptor, increased [Ca2+]i. To assess the participation of inositol triphosphate (IP3) generation, sarcoplasmic/endoplasmic reticulum (SR/ER) Ca2+ depletion, and activation of store-operated Ca2+ entry, we utilized thapsigargin and ryanodine to deplete Ca2+ SR/ER stores and the inhibitory reagents TMB-8 and 2-APB to block IP3 receptors. In each case, these agents inhibited the[Ca2+]i response to agonist stimulation by approximately 50 %. Blockade of L-channels with nifedipine had no significant effect. Increases in ionic strength are known to inhibit the calcium-sensing receptor. We postulate that the CaSR stimulates Ca2+-mediated constriction of the rectal gland artery and diminishes cyclic AMP-mediated salt secretion in rectal gland tubules during non-feeding conditions. When the shark ingests sea water and fish, an increase in blood and interstitial fluid ionic strength inhibits the activity of the calcium-sensing receptor, relaxing the rectal gland artery and permitting salt secretion by the rectal gland tubules.

Hypercalcaemia

2011 ◽  
pp. 642-652
Author(s):  
Ronen Levi ◽  
Justin Silver
Keyword(s):  
Extracellular Fluid ◽  
Immune Functions ◽  
Calcium Sensing Receptor ◽  
Neuromuscular Activation ◽  
Plasma Coagulation ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Calcium Sensing ◽  
Life Threatening

Ionized calcium is essential for several physiological functions, including neuromuscular activation, endocrine and exocrine secretions, integrity of cellular bilayers, plasma coagulation, immune functions and bone metabolism. Extracellular fluid (ECF) calcium is uniquely controlled by its own calcium-sensing receptor, regulating the secretion of parathyroid hormone (PTH), synthesis of 1,25-dihydroxyvitamin D, and the renal reabsorption of filtered calcium (see Chapter 4.1). With the advent of the autoanalyser and routine determination of serum calcium levels, recognition of hypercalcaemia has become common. However, the clinical spectrum of hypercalcaemia varies from a laboratory-detected, asymptomatic mineral disorder to a life-threatening state.

Primary role of volume expansion in stimulation of rectal gland function

1985 ◽  
Vol 248 (5) ◽  
pp. R638-R640 ◽  
Author(s):  
R. Solomon ◽  
M. Taylor ◽  
S. Sheth ◽  
P. Silva ◽  
F. H. Epstein
Keyword(s):  
Plasma Volume ◽  
Plasma Osmolality ◽  
Sodium Concentration ◽  
Chloride Secretion ◽  
Ringer Solution ◽  
Rectal Gland ◽  
Primary Role ◽  
Fourfold Increase ◽  
Gland Function

Chloride secretion by the in vivo rectal gland of the shark is stimulated by the intravascular infusion of salt solutions of varying osmolar and sodium concentration. In a cross-perfused and denervated rectal gland, the infusion of a small amount of a hypertonic salt solution raises plasma osmolality but does not increase plasma volume in the donor fish. Under these conditions, rectal gland chloride secretion is not stimulated. A subsequent infusion of isotonic shark Ringer solution increases plasma volume 50%, decreases plasma osmolality, and produces a fourfold increase in chloride secretion and a threefold decrease in vascular resistance within the gland. Both the vasodilatory and secretory responses also follow the infusion of a hypotonic shark Ringer solution. The data further support the hypothesis that the rectal gland of the shark is involved in the regulation of intravascular volume rather than in osmoregulation.

NFAT regulates calcium-sensing receptor-mediated TNF production

2006 ◽  
Vol 290 (5) ◽  
pp. F1110-F1117 ◽  
Author(s):  
Huda Ismail Abdullah ◽  
Paulina L. Pedraza ◽  
Shoujin Hao ◽  
Karin D. Rodland ◽  
John C. McGiff ◽  
...  
Keyword(s):  
Extracellular Fluid ◽  
Dominant Negative ◽  
Peptide Ligand ◽  
Thick Ascending Limb ◽  
Dependent Manner ◽  
Calcium Sensing Receptor ◽  
Activated T Cells ◽  
Calcium Sensing ◽  
Dependent Activity ◽  
Calcineurin Activity

Because nuclear factor of activated T cells (NFAT) has been implicated in TNF production as well as osmoregulation and salt and water homeostasis, we addressed whether calcium-sensing receptor (CaR)-mediated TNF production in medullary thick ascending limb (mTAL) cells was NFAT dependent. TNF production in response to addition of extracellular Ca2+ (1.2 mM) was abolished in mTAL cells transiently transfected with a dominant-negative CaR construct (R796W) or pretreated with the phosphatidylinositol phospholipase C (PI-PLC) inhibitor U-73122. Cyclosporine A (CsA), an inhibitor of the serine/threonine phosphatase calcineurin, and a peptide ligand, VIVIT, that selectively inhibits calcineurin-NFAT signaling, also prevented CaR-mediated TNF production. Increases in calcineurin activity in cells challenged with Ca2+ were inhibited after pretreatment with U-73122 and CsA, suggesting that CaR activation increases calcineurin activity in a PI-PLC-dependent manner. Moreover, U-73122, CsA, and VIVIT inhibited CaR-dependent activity of an NFAT construct that drives expression of firefly luciferase in transiently transfected mTAL cells. Collectively, these data verify the role of calcineurin and NFAT in CaR-mediated TNF production by mTAL cells. Activation of the CaR also increased the binding of NFAT to a consensus oligonucleotide, an effect that was blocked by U-73122 and CsA, suggesting that a calcineurin- and NFAT-dependent pathway increases TNF production in mTAL cells. This mechanism likely regulates TNF gene transcription as U-73122, CsA, and VIVIT blocked CaR-dependent activity of a TNF promoter construct. Elucidating CaR-mediated signaling pathways that regulate TNF production in the mTAL will be crucial to understanding mechanisms that regulate extracellular fluid volume and salt balance.

scholarly journals Calcium-sensing receptor in GtoPdb v.2021.3

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Daniel Bikle ◽  
Hans Bräuner-Osborne ◽  
Edward M. Brown ◽  
Wenhan Chang ◽  
Arthur Conigrave ◽  
...  
Keyword(s):  
Amino Acids ◽  
Ionic Strength ◽  
Receptor Activation ◽  
Extracellular Ph ◽  
Allosteric Modulators ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Trivalent Cations ◽  
Amino Acid Binding ◽  
Peptide Analogues

The calcium-sensing receptor (CaS, provisional nomenclature as recommended by NC-IUPHAR [47] and subsequently updated [77]) responds to multiple endogenous ligands, including extracellular calcium and other divalent/trivalent cations, polyamines and polycationic peptides, L-amino acids (particularly L-Trp and L-Phe), glutathione and various peptide analogues, ionic strength and extracellular pH (reviewed in [78]). While divalent/trivalent cations, polyamines and polycations are CaS receptor agonists [14, 110], L-amino acids, glutamyl peptides, ionic strength and pH are allosteric modulators of agonist function [36, 47, 61, 108, 109]. Indeed, L-amino acids have been identified as "co-agonists", with both concomitant calcium and L-amino acid binding required for full receptor activation [148, 54]. The sensitivity of the CaS receptor to primary agonists is increased by elevated extracellular pH [18] or decreased extracellular ionic strength [109]. This receptor bears no sequence or structural relation to the plant calcium receptor, also called CaS.

scholarly journals Calcium-sensing receptor (version 2020.5) in the IUPHAR/BPS Guide to Pharmacology Database

2020 ◽  
Vol 2020 (5) ◽  
Author(s):  
Daniel Bikle ◽  
Hans Bräuner-Osborne ◽  
Edward M. Brown ◽  
Wenhan Chang ◽  
Arthur Conigrave ◽  
...  
Keyword(s):  
Amino Acids ◽  
Ionic Strength ◽  
Receptor Activation ◽  
Extracellular Ph ◽  
Allosteric Modulators ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Trivalent Cations ◽  
Amino Acid Binding ◽  
Peptide Analogues

The calcium-sensing receptor (CaS, provisional nomenclature as recommended by NC-IUPHAR [46] and subsequently updated [76]) responds to multiple endogenous ligands, including extracellular calcium and other divalent/trivalent cations, polyamines and polycationic peptides, L-amino acids (particularly L-Trp and L-Phe), glutathione and various peptide analogues, ionic strength and extracellular pH (reviewed in [77]). While divalent/trivalent cations, polyamines and polycations are CaS receptor agonists [14, 109], L-amino acids, glutamyl peptides, ionic strength and pH are allosteric modulators of agonist function [35, 46, 60, 107, 108]. Indeed, L-amino acids have been identified as "co-agonists", with both concomitant calcium and L-amino acid binding required for full receptor activation [147, 53]. The sensitivity of the CaS receptor to primary agonists is increased by elevated extracellular pH [17] or decreased extracellular ionic strength [108]. This receptor bears no sequence or structural relation to the plant calcium receptor, also called CaS.

Role of the calcium-sensing receptor in parathyroid gland physiology

2004 ◽  
Vol 286 (6) ◽  
pp. F1005-F1011 ◽  
Author(s):  
Randolph A. Chen ◽  
William G. Goodman
Keyword(s):  
Parathyroid Gland ◽  
Calcium Concentration ◽  
Physiological Role ◽  
Receptor Expression ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Current Review ◽  
Recent Developments ◽  
Gland Function

The calcium-sensing receptor (CaSR) represents the molecular mechanism by which parathyroid cells detect changes in blood ionized calcium concentration and modulate parathyroid hormone (PTH) secretion to maintain serum calcium levels within a narrow physiological range. Much has been learned in recent years about the diversity of signal transduction through the CaSR and the various factors that affect receptor expression. Beyond its classic role as a determinant of calcium-regulated PTH secretion, signaling through the CaSR also influences both gene transcription and cell proliferation in parathyroid cells. The CaSR thus serves a broad physiological role by integrating several distinct aspects of parathyroid gland function. The current review summarizes recent developments that enhance our understanding of the CaSR and its fundamental importance in parathyroid gland physiology.

scholarly journals Calcium-sensing receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Daniel Bikle ◽  
Hans Bräuner-Osborne ◽  
Edward M. Brown ◽  
Wenhan Chang ◽  
Arthur Conigrave ◽  
...  
Keyword(s):  
Amino Acids ◽  
Ionic Strength ◽  
Receptor Activation ◽  
Extracellular Ph ◽  
Allosteric Modulators ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Trivalent Cations ◽  
Amino Acid Binding ◽  
Peptide Analogues

The calcium-sensing receptor (CaS, provisional nomenclature as recommended by NC-IUPHAR [44]) responds to multiple endogenous ligands, including extracellular calcium and other divalent/trivalent cations, polyamines and polycationic peptides, L-amino acids (particularly L-Trp and L-Phe), glutathione and various peptide analogues, ionic strength and extracellular pH (reviewed in [74]). While divalent/trivalent cations, polyamines and polycations are CaS receptor agonists [14, 106], L-amino acids, glutamyl peptides, ionic strength and pH are allosteric modulators of agonist function [34, 44, 58, 104, 105]. Indeed, L-amino acids have been identified as "co-agonists", with both concomitant calcium and L-amino acid binding required for full receptor activation [143, 51]. The sensitivity of the CaS receptor to primary agonists is increased by elevated extracellular pH [17] or decreased extracellular ionic strength [105]. This receptor bears no sequence or structural relation to the plant calcium receptor, also called CaS.

Abstract #543 Teriparatide-Induced Hypercalcemic Crisis in a Patient on Lithium: Overwhelming the Calcium Sensing Receptor

2018 ◽  
Vol 24 ◽  
pp. 130-131
Author(s):  
Pratibha Abraham ◽  
Muhammad Siddiqui ◽  
Deepashree Gupta ◽  
Stewart Albert
Keyword(s):  
Calcium Sensing Receptor ◽  
Hypercalcemic Crisis ◽  
Calcium Sensing
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