Calcium-sensing receptor (CaSR): Pharmacological properties and signaling pathways

Calcium Promotes Human Gastric Cancer via a Novel Coupling of Calcium-Sensing Receptor and TRPV4 Channel

“…Third, calcium and CaSR function are important for gastric cancer growth and metastasis both in vitro and in vivo. Fourth, CaSR stimulation in gastric cancer cells activates TRPV4, which in turn mediates Ca 2þ entry to increase [Ca 2þ ] cyt and consequent activation of AKT and b-catenin, a well-known oncogenic pathway (5,(21)(22)(23). Fifth, CaSR exhibits aberrant functions in gastric cancer cells as compared to nontumorigenic gastric cells.…”

“…CaSR activation stimulates [Ca 2þ ] cyt rise, as well as PI3K/AKT, b-catenin, and MAPK signaling (5,21,23,24), all of which are involved in malignant progression of cancers. Ca 2þ signaling is well recognized to regulate proliferation, migration, epithelial mesenchymal transition (EMT), and malignant transformation (22,26 (29).…”

Knockin mouse with mutant Gα11 mimics human inherited hypocalcemia and is rescued by pharmacologic inhibitors

“…The clinical findings of ADH2 implicate the involvement of the calcium-sensing receptor (CASR), which can couple to several G proteins, including Gα 11 , and is expressed on the surface of the parathyroid chief cells. Activation of the CASR suppresses production and secretion of parathyroid hormone (PTH), a principal calcium-regulating hormone that increases blood calcium through effects on bone and kidney (15,16). Activating mutations in CASR cause ADH1, in which hypocalcemia is observed with inappropriately low circulating PTH levels, resembling the clinical phenotype of ADH2 (17).…”

Positive Allosteric Modulation of the Calcium-sensing Receptor by Physiological Concentrations of Glucose

“…For example, calcimimetics bind to the transmembrane domain and stabilize the receptor in the active form (5). Conversely, NPS-2143, an allosteric inhibitor of CaSR, binds to the transmembrane domain of CaSR and may stabilize the inactive conformation of CaSR (7).…”

“…In addition to parathyroid glands, CaSR is expressed in tissues involved in the regulation of Ca 2ϩ homeostasis including kidney, intestine, and bone. This receptor is also expressed in various other tissues and organs including neurons and glial cells (3) and may modulate the function of these cells (3)(4)(5) , amino acids, polypeptides, aminoglycosides, and polyamines (4,5). Among them, a principal agonist for CaSR is Ca 2ϩ , which binds to a pocket in the VFTD (6).…”