The Calcium-Sensing Receptor: from Physiology to Pharmacology

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About this Research Topic

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Background

The Calcium-Sensing Receptor (CaSR) is a G-Protein coupled receptor that has several unique properties. Its main physiological ligand is ionized Ca2+, but it also “senses” other cations such as Mg2+, or polyamines such as spermine while the pharmacological activity of the CaSR is influenced e.g. by allosteric modulators such as certain synthetic small molecules, but also amino acids, phosphate and pH. It signals through various pathways depending on the cell it is expressed in and the ligand that is bound to it. This versatility accounts for the manifold roles that have been identified for this multifaceted protein. Its "classical" function is the control of physiological calcium homeostasis via regulation of parathyroid hormone secretion and calcium-reabsorption in the kidneys. However, the CaSR is also involved in multiple other processes, including bone metabolism, neuronal differentiation, smooth muscle contraction, as well as pathologies such as inflammation in airways and the gut, or pulmonary hypertension. A fascinating latest aspect of the CaSR is its regulation of protein expression levels via microRNA.

The above-mentioned versatility of the CaSR and its unique physiological and pharmacological properties makes it an interesting object of study. The goal of the present Research Topic is thus to provide a comprehensive overview of the most recent advances in CaSR physiology and its linked unique pharmacological properties, with a special focus on how these advances in our understanding of the CaSR are currently translated into novel therapeutic approaches. We invite leading experts as well as young researchers in the CaSR field to present their most recent findings in basic, translational and clinical research on
a) the receptor's physiological functions in the body and how it links this to (or its relationships with)
b) how these functions are currently targeted and investigated for novel (pharmaco-)therapies.

We especially welcome contributions either in the form of original research articles, short communications, reviews or shorter perspective articles. We aim to achieve a balance of comprehensive review articles on the main physiological roles of the CaSR and its related pharmacological aspects as well as original research, to show this bridge between the unique physiology of the CaSR and the applicability of this knowledge in developing CaSR-targeted therapies.
Relevant topics include but are not restricted to:
- Molecular actions of the CaSR and its ligands
- CaSR pharmacology and CaSR-targeting drugs
- Cellular mechanisms and signalling of the CaSR
- Physiological and pathophysiological roles of the CaSR in specific organs or tissues, with specific emphasis on non-mineral ion homeostasis related pathologies such as: inflammation, developmental biology, water handling and glucose metabolism
- CaSR-related diseases
- Translational and clinical research in (novel) CaSR-targeted treatments.

Keywords: calcium-sensing receptor, therapeutic target, CaSR signalling, CaSR antagonist, CaSR agonist

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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