Premium
Engendering biased signalling from the calcium‐sensing receptor for the pharmacotherapy of diverse disorders
Author(s) -
Leach K,
Sexton P M,
Christopoulos A,
Conigrave A D
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12420
Subject(s) - allosteric regulation , calcium sensing receptor , receptor , signalling , functional selectivity , signal transduction , ligand (biochemistry) , extracellular , calcium signaling , intracellular , microbiology and biotechnology , g protein coupled receptor , biology , cell type , cell signaling , neuroscience , chemistry , cell , calcium , biochemistry , calcium metabolism , organic chemistry
The human calcium-sensing receptor (CaSR) is widely expressed in the body, where its activity is regulated by multiple orthosteric and endogenous allosteric ligands. Each ligand stabilizes a unique subset of conformational states, which enables the CaSR to couple to distinct intracellular signalling pathways depending on the extracellular milieu in which it is bathed. Differential signalling arising from distinct receptor conformations favoured by each ligand is referred to as biased signalling. The outcome of CaSR activation also depends on the cell type in which it is expressed. Thus, the same ligand may activate diverse pathways in distinct cell types. Given that the CaSR is implicated in numerous physiological and pathophysiological processes, it is an ideal target for biased ligands that could be rationally designed to selectively regulate desired signalling pathways in preferred cell types.