Engendering biased signalling from the calcium-sensing receptor for the pharmacotherapy of diverse disorders

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1142 - 1155
Number of pages14
JournalBritish Journal of Pharmacology
Volume171
Issue number5
DOIs
Publication statusPublished - 2014

Cite this

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title = "Engendering biased signalling from the calcium-sensing receptor for the pharmacotherapy of diverse disorders",
abstract = "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.",
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Engendering biased signalling from the calcium-sensing receptor for the pharmacotherapy of diverse disorders. / Leach, Katherine; Sexton, Patrick; Christopoulos, Arthur; Conigrave, Arthur.

In: British Journal of Pharmacology, Vol. 171, No. 5, 2014, p. 1142 - 1155.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Engendering biased signalling from the calcium-sensing receptor for the pharmacotherapy of diverse disorders

AU - Leach, Katherine

AU - Sexton, Patrick

AU - Christopoulos, Arthur

AU - Conigrave, Arthur

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AB - 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.

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