Inhibition of the calcium-sensing receptor by extracellular phosphate ions and by intracellular phosphorylation

Patricia P Centeno; Lenah S Binmahfouz; Khaleda Alghamdi; Donald T Ward

doi:10.3389/fphys.2023.1154374

Inhibition of the calcium-sensing receptor by extracellular phosphate ions and by intracellular phosphorylation

Front Physiol. 2023 Mar 31:14:1154374. doi: 10.3389/fphys.2023.1154374. eCollection 2023.

Authors

Patricia P Centeno¹, Lenah S Binmahfouz^{1

2}, Khaleda Alghamdi^{1

2}, Donald T Ward¹

Affiliations

¹ Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.
² Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

As both a sensor of extracellular calcium (Ca²⁺ _o) concentration and a key controller of Ca²⁺ _o homeostasis, one of the most interesting properties of the calcium-sensing receptor (CaR) is its sensitivity to, and modulation by, ions and small ligands other than Ca²⁺. There is emerging evidence that extracellular phosphate can act as a partial, non-competitive CaR antagonist to modulate parathyroid hormone (PTH) secretion, thus permitting the CaR to integrate mineral homeostasis more broadly. Interestingly, phosphorylation of certain intracellular CaR residues can also inhibit CaR responsiveness. Thus, negatively charged phosphate can decrease CaR activity both extracellularly (via association with arginine) and intracellularly (via covalent phosphorylation).

Keywords: calcium-sensing receptor; parathyroid hormone; phosphate-sensing; receptor phosphorylation; secondary hyperparathyroidism.

Publication types

Review