Intercellular communication mediated by the extracellular calcium-sensing receptor

Agonist-evoked, intracellular Ca2+-signalling events are associated with ac tive extrusion of Ca2+ across the plasma membrane, implying a local increas e in Ca2+ concentration ([Ca2+]) at the extracellular face of the cell. The possibility that these external [Ca2+] changes may have specific physiolog ical functions has received little consideration in the past. Here we show that, at physiological ambient [Ca2+], Ca2+ mobilization in one cell produc es an extracellular signal that can be detected in nearby cells expressing the extracellular Ca2+-sensing receptor (CaR), a cell-surface receptor for divalent cations with a widespread tissue distribution. The Can may therefo re mediate a universal form of intercellular communication that allows cell s to be informed of the Ca2+-signalling status of their neighbours.