Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics.

ABSTRACT:

Background and purpose

Clinical use of cinacalcet in hyperparathyroidism is complicated by its tendency to induce hypocalcaemia, arising partly from activation of calcium-sensing receptors (CaS receptors) in the thyroid and stimulation of calcitonin release. CaS receptor allosteric modulators that selectively bias signalling towards pathways that mediate desired effects [e.g. parathyroid hormone (PTH) suppression] rather than those mediating undesirable effects (e.g. elevated serum calcitonin), may offer better therapies.

Experimental approach

We characterized the ligand-biased profile of novel calcimimetics in HEK293 cells stably expressing human CaS receptors, by monitoring intracellular calcium (Ca(2+) i ) mobilization, inositol phosphate (IP)1 accumulation, ERK1/2 phosph

SUBMITTER: Cook AE 

PROVIDER: S-EPMC4280977 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature