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Wellcome Prize Lecture. Cell surface, ion-sensing receptors
1School of Biological Sciences, University of Manchester, UK. riccardi@man.ac.uk
Experimental Physiology
|October 24, 2002
Summary
The calcium-sensing receptor (CaR) directly regulates kidney function and calcium homeostasis. It also plays roles outside mineral ion balance, responding to various cations and modulators.
Area of Science:
- Physiology
- Molecular Biology
- Biochemistry
Background:
- Extracellular calcium ([Ca2+]o) concentration significantly impacts kidney function.
- The calcium-sensing receptor (CaR) directly modulates parathyroid and kidney function, independent of calciotropic hormones.
- CaR is expressed in various tissues beyond calcium homeostasis, suggesting roles in local ionic regulation.
Discussion:
- CaR belongs to the type III G protein-coupled receptor (GPCR) family.
- The receptor exhibits low affinity for Ca2+ and sensitivity to net cationic charge, activated by various cations like Mg2+ and polyvalent cations.
- CaR activation can be allosterically modulated by ionic strength, L-amino acids, and pharmacological agents.
Key Insights:
- CaR is a crucial regulator of calcium homeostasis.
- The receptor's broad sensitivity allows it to sense diverse ionic environments.
- CaR's presence in non-homeostatic tissues indicates novel physiological functions.
Outlook:
- Further research is needed to elucidate CaR's function in non-homeostatic tissues.
- Understanding CaR modulation could lead to new therapeutic strategies.
- Investigating CaR's role in local ionic regulation may reveal new physiological mechanisms.