Intercellular communication mediated by the extracellular calcium-sensing receptor

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