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10.1124/pr.119.018531 http://scihub22266oqcxt.onion/10.1124/pr.119.018531 32467152!7116503!32467152     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Pharmacol+Rev 2020 ; 72 (3): 558-604 Nephropedia Template TP {{tp|p=32467152|t=2020. International Union of Basic and Clinical Pharmacology CVIII Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function |pdf=|usr=}}{{32467152}} gab.com Text International Union of Basic and Clinical Pharmacology CVIII Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function JO: Pharmacol Rev http://www.kidney.de/pget.php?&tw=1&pmid=32467152 #FOAvip The calcium-sensing receptor (CaSR) is a class C G protein-coupled receptor that responds to multiple endogenous agonists and allosteric modulators, including divalent and trivalent cations, L-amino acids, gamma-glutamyl peptides, polyamines, polycationic peptides, and protons. The CaSR plays a critical role in extracellular calcium (Ca(2+) (o)) homeostasis, as demonstrated by the many naturally occurring mutations in the CaSR or its signaling partners that cause Ca(2+) (o) homeostasis disorders. However, CaSR tissue expression in mammals is broad and includes tissues unrelated to Ca(2+) (o) homeostasis, in which it, for example, regulates the secretion of digestive hormones, airway constriction, cardiovascular effects, cellular differentiation, and proliferation. Thus, although the CaSR is targeted clinically by the positive allosteric modulators (PAMs) cinacalcet, evocalcet, and etelcalcetide in hyperparathyroidism, it is also a putative therapeutic target in diabetes, asthma, cardiovascular disease, and cancer. The CaSR is somewhat unique in possessing multiple ligand binding sites, including at least five putative sites for the "orthosteric" agonist Ca(2+) (o), an allosteric site for endogenous L-amino acids, two further allosteric sites for small molecules and the peptide PAM, etelcalcetide, and additional sites for other cations and anions. The CaSR is promiscuous in its G protein-coupling preferences, and signals via G(q/11), G(i/o), potentially G(12/13), and even G(s) in some cell types. Not surprisingly, the CaSR is subject to biased agonism, in which distinct ligands preferentially stimulate a subset of the CaSR's possible signaling responses, to the exclusion of others. The CaSR thus serves as a model receptor to study natural bias and allostery. SIGNIFICANCE STATEMENT: The calcium-sensing receptor (CaSR) is a complex G protein-coupled receptor that possesses multiple orthosteric and allosteric binding sites, is subject to biased signaling via several different G proteins, and has numerous (patho)physiological roles. Understanding the complexities of CaSR structure, function, and biology will aid future drug discovery efforts seeking to target this receptor for a diversity of diseases. This review summarizes what is known to date regarding key structural, pharmacological, and physiological features of the CaSR. Twit Text FOAVip International Union of Basic and Clinical Pharmacology CVIII Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function ????Pharmacol Rev http://www.kidney.de/pget.php?&tw=1&pmid=32467152 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32467152 #FOAvip English Wikipedia <ref>{{Cite pmid|32467152}}</ref> International Union of Basic and Clinical Pharmacology CVIII Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function #MMPMID32467152 Leach K; Hannan FM; Josephs TM; Keller AN; Moller TC; Ward DT; Kallay E; Mason RS; Thakker RV; Riccardi D; Conigrave AD; Brauner-Osborne H Pharmacol Rev 2020[Jul]; 72 (3): 558-604 PMID32467152show ga The calcium-sensing receptor (CaSR) is a class C G protein-coupled receptor that responds to multiple endogenous agonists and allosteric modulators, including divalent and trivalent cations, L-amino acids, gamma-glutamyl peptides, polyamines, polycationic peptides, and protons. The CaSR plays a critical role in extracellular calcium (Ca(2+) (o)) homeostasis, as demonstrated by the many naturally occurring mutations in the CaSR or its signaling partners that cause Ca(2+) (o) homeostasis disorders. However, CaSR tissue expression in mammals is broad and includes tissues unrelated to Ca(2+) (o) homeostasis, in which it, for example, regulates the secretion of digestive hormones, airway constriction, cardiovascular effects, cellular differentiation, and proliferation. Thus, although the CaSR is targeted clinically by the positive allosteric modulators (PAMs) cinacalcet, evocalcet, and etelcalcetide in hyperparathyroidism, it is also a putative therapeutic target in diabetes, asthma, cardiovascular disease, and cancer. The CaSR is somewhat unique in possessing multiple ligand binding sites, including at least five putative sites for the "orthosteric" agonist Ca(2+) (o), an allosteric site for endogenous L-amino acids, two further allosteric sites for small molecules and the peptide PAM, etelcalcetide, and additional sites for other cations and anions. The CaSR is promiscuous in its G protein-coupling preferences, and signals via G(q/11), G(i/o), potentially G(12/13), and even G(s) in some cell types. Not surprisingly, the CaSR is subject to biased agonism, in which distinct ligands preferentially stimulate a subset of the CaSR's possible signaling responses, to the exclusion of others. The CaSR thus serves as a model receptor to study natural bias and allostery. SIGNIFICANCE STATEMENT: The calcium-sensing receptor (CaSR) is a complex G protein-coupled receptor that possesses multiple orthosteric and allosteric binding sites, is subject to biased signaling via several different G proteins, and has numerous (patho)physiological roles. Understanding the complexities of CaSR structure, function, and biology will aid future drug discovery efforts seeking to target this receptor for a diversity of diseases. This review summarizes what is known to date regarding key structural, pharmacological, and physiological features of the CaSR. |Animals[MESH] |Binding Sites[MESH] |GTP-Binding Proteins/metabolism[MESH] |Humans[MESH] |Models, Molecular[MESH] |Receptors, Calcium-Sensing/*agonists/*antagonists & inhibitors/chemistry/metabolism[MESH] |Signal Transduction[MESH]International Union of Basic and Clinical Pharmacology CVIII Calcium(epmc).pdf DeepDyve Pubget Overpricing