Physiological significance Of L-arnino acid sensing by extracellular Ca2+-sensing receptors

The calcium-sensing receptor is a multimodal, multimetabolic sensor that mediates the feedback-dependent control of whole body calcium metabolism. Remarkably, in addition to its role in Ca-o(2+) (extracellular Ca2+) sensing, the CaR (Ca2+-sensing receptor) also responds to L-amino acids. L-amino acids appear to activate, predominantly, a signalling pathway coupled with intracellular Ca2+ mobilization, require a threshold concentration of Ca-o(2+) for efficacy and sensitize the receptor to activation by Ca-o(2+). Here, we review the evidence that the CaR, like other closely related members of the class 3 GPCR (G-protein-coupled receptor) family including GPRC6A, is a broad-spectrum amino acid-sensing receptor, consider the nature of the signalling response to amino acids and discuss its physiological significance.