title: Secretion in alveolar type II cells at the interface of constitutive and regulated exocytosis.
abstract: Long-term, simultaneous, measurements of cytoplasmic free Ca(2+) concentrations and single exocytotic fusion events in surfactant-secreting type II cells were performed. All fusion (constitutive, phorbol ester-induced, and agonist-induced) was Ca(2+)-dependent. Kinetic analysis revealed that agonist (adenosine triphosphate [ATP])-induced fusion exhibited a kinetic pattern that correlated well with the Ca(2+) signal. The effects of Ca(2+) release from intracellular stores (early) and Ca(2+) entry (late) could be demonstrated for the first time by dissecting the slow (10-to-15-min) fusion response to ATP into these two components. Bath Ba(2+) or Sr(2+) could replace Ca(2+) to elicit a fusion response in thapsigargin-pretreated cells lacking ATP-induced Ca(2+) release from stores. Although the late response was partially inhibited by interrupting the phospholipase D-protein kinase C axis, a high Ca(2+) dependence of the entire secretory course was demonstrated by a significant correlation between the integrated Ca(2+) signal and the fusion response. There was also a highly significant correlation between constitutive and ATP-stimulated fusion activity in individual cells. We propose a common mechanistic model for all types of fusion in this slow secretory cell, in which constitutive and regulated forms of exocytosis are subject to the same principles of regulation.
authors.affiliation: Department of Physiology, University of Innsbruck, Innsbruck, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Frick
authors.forename: S
authors.initials: S
authors.lastname: Eschertzhuber
authors.forename: T
authors.initials: T
authors.lastname: Haller
authors.forename: N
authors.initials: N
authors.lastname: Mair
authors.forename: P
authors.initials: P
authors.lastname: Dietl
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000440:Butanols / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002413:Cations, Divalent / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology*; D008297:Male; D008561:Membrane Fusion / Q000502:physiology*; D011493:Protein Kinase C / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022142:Secretory Vesicles / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000440:Butanols; D002413:Cations, Divalent; D002614:Chelating Agents; D004075:Diglycerides; C085112:2-nitrophenyl-EGTA; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium