Calcimimetic and calcilytic therapies for inherited disorders of the calcium-sensing receptor signalling pathway.

ABSTRACT: The calcium-sensing receptor (CaS receptor) plays a pivotal role in extracellular calcium homeostasis, and germline loss-of-function and gain-of-function mutations cause familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemia (ADH), respectively. CaS receptor signal transduction in the parathyroid glands is probably regulated by G-protein subunit α₁₁ (Gα₁₁ ) and adaptor-related protein complex-2 σ-subunit (AP2σ), and recent studies have identified germline mutations of these proteins as a cause of FHH and/or ADH. Calcimimetics and calcilytics are positive and negative allosteric modulators of the CaS receptor that have potential efficacy for symptomatic forms of FHH and ADH. Cellular studies have demonstrated that these compounds correct signa

SUBMITTER: Hannan FM 

PROVIDER: S-EPMC6177618 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature