Pepsinogen stores (top) are excreted in response to an increase in extracellular Ca 2+ (bottom).

Calcium just got a promotion. Findings by Caroppo et al. (page 111) reveal that in addition to its many roles inside the cell, Ca2+ has a distinct extracellular purpose: it acts via a Ca2+receptor (CaR) to regulate the function of gastric epithelial cells.

It has been known for some time that extracellular Ca2+ can be sensed by the CaR. The team noted that a Ca2+ gradient was generated outside gastric cells after cholinergic stimulation with carbachol, which mimics a signal received during digestion processes. Ca2+ levels increased on the apical side and decreased on the basolateral side, and prompted secretion of pepsinogen. Proteolytic cleavage of pepsinogen yields the digestive enzyme pepsin.

It is well known that carbachol boosts intracellular Ca2+ in gastric cells, and a resultant increase in extracellular Ca2+ is no surprise. But the authors found that extracellular Ca2+ was both necessary and sufficient for the induction of pepsinogen secretion.

Perhaps cells economize by using a single messenger, calcium, both inside and outside of the cell. In this way, the authors speculate, cells can use the raised Ca2+ levels that are present outside cells during intracellular Ca2+ signaling events to control necessary functions. ▪