Calcium acts as a first messenger through the calcium-sensing receptor in the cardiovascular system

It is well known that calcium is an important second messenger in the cardiovascular system. However, recent studies suggest that, in addition to its many functions as an intracellular messenger, Ca(2+) may also be an extracellular first messenger through the calcium-sensing receptor (CaR). The CaR belongs to family C of the G-protein-coupled receptors, which are also known as seven transmembrane domain receptors. The CaR receptor is expressed in all major organs involved in Ca(2+) homeostasis. Furthermore, increasing evidence suggests that the CaR is also involved in regulating various cellular functions in tissues not involved in Ca(2+) homeostasis. Recently, expression of a functional CaR has also been reported in crucial components of the cardiovascular system. It has previously been shown that the CaR is functionally expressed in the atria and ventricle of the rat heart. In blood vessels, the CaR protein was first reported in perivascular nerves of rat mesenteric resistance arteries, and was proposed to modulate myogenic tone in the arteries. Since then, the CaR has been detected in homogenates of whole vessels from rat subcutaneous small arteries and in endothelial cells from rat mesenteric and porcine coronary arteries. Furthermore, a recent report demonstrated that the CaR is present in endothelial cells from human aorta and that it stimulates production of nitric oxide in these cells. Taken together, these results indicate that the CaR present in blood vessels may have a physiological role in modulation of arterial blood pressure. This review discusses CaR expression and function, with a focus on the role of the CaR in the cardiovascular system.