Working Outside the Cell

Abstract

Many signaling molecules interact with cell surface receptors to mobilize calcium from intracellular stores, eliciting transient changes in the concentration of intracellular calcium ([Ca 2+ ] i ), which acts as a second messenger. Mobilized cytoplasmic Ca 2+ extruded through plasma membrane Ca 2+ ATPases can increase local extracellular Ca 2+ concentration [Ca 2+ ] o, whereas store-operated Ca 2+ entry can lead to a localized decrease in [Ca 2+ ] o . Indeed, in gastric epithelial cells, the cholinergic agonist carbachol elicits a simultaneous increase in lumenal [Ca 2+ ] o and decrease in serosal [Ca 2+ ] o , because of the polarized distribution of Ca 2+ -handling molecules. Using a proteolytic assay to measure pepsinogen secretion, and ion-sensitive microelectrodes to measure pH and [Ca 2+ ], Caroppo et al. investigated the effects of changing [Ca 2+ ] o on alkaline secretion and pepsinogen secretion in isolated frog gastric mucosa. Simultaneous changes in lumenal and serosal [Ca 2+ ] o comparable to those elicited by carbachol stimulated comparable secretion of pepsinogen and changes in gastric gland lumenal pH. Increasing only lumenal [Ca 2+ ] o had a smaller effect on secretion, whereas decreasing serosal [Ca 2+ ] o alone was ineffective. Pharmacological analysis implicated a previously identified extracellular Ca 2+ receptor (CaR) in the response; moreover, citrate, added to buffer lumenal [Ca 2+ ] o , prevented both the carbachol-dependent increase in lumenal [Ca 2+ ] o and alkaline and pepsinogen secretion. In contrast, stimulating CaR pharmacologically or increasing lumenal [Ca 2+ ] o did not affect [Ca 2+ ] i , as measured either with intracellular microelectrodes or indirectly through activation of a Ca 2+ -sensitive K + current. Thus, the authors propose that, in this system, changes in [Ca 2+ ] o after Ca 2+ mobilization from intracellular stores can act as a third messenger to stimulate secretion. R. Caroppo, A. Gerbino, G. Fistetto, M. Colella, L. Debellis, A. M. Hofer, S. Curci, Extracellular calcium acts as a "third messenger" to regulate enzyme and alkaline secretion. J. Cell Biol . 166 , 111-119 (2004). [Abstract] [Full Text]