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• W2091291205 startingPage "1131" @default.
• W2091291205 abstract "The calcium-sensing receptor (CaR) belongs to the G protein-coupled receptor superfamily, with a characteristic structure consisting of seven transmembrane helices, an intracellular C-terminal and an extracellular N terminal domain. The primary physiological function of the CaR is the maintenance of constant blood Ca²⁺ levels, as a result of its ability to sense very small changes in extracellular Ca²⁺ (Ca²⁺_o). Nevertheless, in addition to being expressed in tissues involved in Ca²⁺_o homeostasis, the CaR is also expressed in tissues not involved in mineral homeostasis, suggestive of additional physiological functions. Numerous agonists and modulators of the CaR are now known in addition to Ca²⁺_o, including various divalent and trivalent cations, aromatic l-amino acids, polyamines, and aminoglycoside antibiotics. The signaling of the CaR is also regulated by extracellular pH and ionic strength. The activated CaR couples mainly to the phospholipase Cβ and extracellular signal-regulated kinase 1/2 signaling pathways, and it decreases intracellular cAMP levels, leading to various physiological effects. The recent identification of synthetic allosteric modulators of the CaR has opened up a new field of research possibilities. Calcimimetics and calcilytics, which increase and decrease agonist signaling via the CaR, respectively, may facilitate the manipulation of the CaR and thus aid in further investigations of its precise signaling. These allosteric modulators, as well as strontium, have been demonstrated to have therapeutic potential for the treatment of disorders involving the CaR. This review discusses the various agonists and modulators of the CaR, differences in their binding and signaling, and their roles as therapeutics in various diseases." @default.
• W2091291205 created "2016-06-24" @default.
• W2091291205 creator A5000161123 @default.
• W2091291205 creator A5004453256 @default.
• W2091291205 creator A5056479973 @default.
• W2091291205 creator A5076711449 @default.
• W2091291205 date "2009-09-24" @default.
• W2091291205 modified "2023-10-16" @default.
• W2091291205 title "Agonists and Allosteric Modulators of the Calcium-Sensing Receptor and Their Therapeutic Applications" @default.
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