Cellular activation by Ca2+ release from stores in the endoplasmic reticulum but not by increased free Ca2+ in the cytosol

Ca2+ release from intracellular stores and/or transmembrane influx can incr ease the cytosolic free Ca2+ concentration ([Ca2+](i)). Such changes in [Ca 2+](i) might transduce signals regulating transcription, motility, secretio n, and so on. Surfactant secretagogues such as ATP and ionomycin stimulate the release and transmembrane influx of Ca2+, both of which increase [Ca2+] (i). The addition of surfactant protein A (SP-A) or depleting cellular Ca2 inhibited both surfactant secretion and Ca2+ transients. Current results s uggest that Ca2+ signalling stimulates surfactant secretion by type II pneu mocytes, but not via increased [Ca2+](i). Treatment of cells with a Ca2+ ch elator, bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid acetoxymethy l ester (BAPTA-AM), stimulated secretion but decreased [Ca2+](i). Adding SP -A or depleting Ca2+ inhibited BAPTA-AM-induced secretion. When studied dir ectly, Ca2+ in the endoplasmic reticulum store ([Ca2+](i)) decreased in res ponse to BAPTA, ionomycin and thapsigargin, and increased in response to SP -A. Phorbol eater (PMA) induced surfactant secretion without altering [Ca2](i) or [Ca2+](i) and was unaffected by Ca2+ depletion. The addition of PMA to Ca2+-releasing secretagogues increased secretion, but combining two Ca2 +-releasing secretagogues did not. These results suggest that (1) Ca2+ sign alling of type II cell surfactant secretion reflects changes in [Ca2+](i), not [Ca2+](i), (2) PMA elicits secretion differently from Ca2+-releasing se cretagogues, and (3) SP-A inhibits secretion by enhancing Ca2+ sequestratio n within endoplasmic reticulum stores. Whether other cell types signal via changes in [Ca2+](i), is unknown.