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. 1999 Nov 15;344(Pt 1):39–46.

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

D S Strayer 1, J B Hoek 1, A P Thomas 1, M K White 1
PMCID: PMC1220611  PMID: 10548531

Abstract

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

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Selected References

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