Calcium signaling in human airway goblet cells following purinergic activation.
Calcium signaling in human airway goblet cells following purinergic activation.
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嘌呤能激活后人气道杯状细胞中的钙信号传导。
DOI：
10.1152/ajplung.00081.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Davis,CWilliam
中科院分区：
文献类型：
--
作者：
Rossi,AndreaH;Salmon,WendyC;Chua,Michael;Davis,CWilliam
Despite the general importance of Ca2+signaling in signal transduction, and of goblet cell mucin hypersecretion in inflammatory pulmonary diseases, measurement of airway goblet cell intracellular Ca2+(Ca\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(_{\mathrm{i}}^{2{+}}\) \end{document}) has not been reported. In this article, we describe the results of experiments measuring Ca\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(_{\mathrm{i}}^{2{+}}\) \end{document} in primary cultures of human bronchial goblet cells after stimulation with the purinergic agonist adenosine 5′-O-(3-thiotriphosphate) (ATPγS) and phorbol 12-myristate 13-acetate (PMA). Ca2+signaling in human goblet cells after purinergic stimulation follows the classic paradigm of a Ca\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(_{\mathrm{i}}^{2{+}}\) \end{document} transient from a basal activity of 110 nM to a peak response of 260.1 ± 41.2 nM within 2 min, followed by a long superbasal plateau (155.3 ± 0.2 nM) between 10 and 15 min. The rise in Ca\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(_{\mathrm{i}}^{2{+}}\) \end{document} appears to result from a mobilization of intracellular stores, because the transient was nearly abolished by inhibition of PLC with the phosphatidylinositol-specific PLC inhibitor U-73122, and it was not affected significantly by removal of extracellular Ca2+. Loading goblet cells with BAPTA inhibited the ATPγS-induced Ca2+transient by 86.0 ± 13.1%, relative to control. Finally, in contrast to the massive effects of high doses of PMA (300 nM) on mucin secretion from goblet cells, phorbol ester stimulated a small (27.1 ± 7% of the ATPγS control peak), brief rise in Ca\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(_{\mathrm{i}}^{2{+}}\) \end{document}. This diminutive signal likely denotes a local Ca2+gradient, which may be associated with the mucin granule exocytotic process.
Despite the general importance of Ca2+signaling in signal transduction, and of goblet cell mucin hypersecretion in inflammatory pulmonary diseases, measurement of airway goblet cell intracellular Ca2+(Ca\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(_{\mathrm{i}}^{2{+}}\) \end{document}) has not been reported. In this article, we describe the results of experiments measuring Ca\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(_{\mathrm{i}}^{2{+}}\) \end{document} in primary cultures of human bronchial goblet cells after stimulation with the purinergic agonist adenosine 5′-O-(3-thiotriphosphate) (ATPγS) and phorbol 12-myristate 13-acetate (PMA). Ca2+signaling in human goblet cells after purinergic stimulation follows the classic paradigm of a Ca\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(_{\mathrm{i}}^{2{+}}\) \end{document} transient from a basal activity of 110 nM to a peak response of 260.1 ± 41.2 nM within 2 min, followed by a long superbasal plateau (155.3 ± 0.2 nM) between 10 and 15 min. The rise in Ca\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(_{\mathrm{i}}^{2{+}}\) \end{document} appears to result from a mobilization of intracellular stores, because the transient was nearly abolished by inhibition of PLC with the phosphatidylinositol-specific PLC inhibitor U-73122, and it was not affected significantly by removal of extracellular Ca2+. Loading goblet cells with BAPTA inhibited the ATPγS-induced Ca2+transient by 86.0 ± 13.1%, relative to control. Finally, in contrast to the massive effects of high doses of PMA (300 nM) on mucin secretion from goblet cells, phorbol ester stimulated a small (27.1 ± 7% of the ATPγS control peak), brief rise in Ca\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(_{\mathrm{i}}^{2{+}}\) \end{document}. This diminutive signal likely denotes a local Ca2+gradient, which may be associated with the mucin granule exocytotic process.