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首页> 外文期刊>Cellular Signalling >Modulation of thapsigargin-induced calcium mobilisation by cyclic AMP-elevating agents in human lymphocytes is insensitive to the action of the protein kinase A inhibitor H-89
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Modulation of thapsigargin-induced calcium mobilisation by cyclic AMP-elevating agents in human lymphocytes is insensitive to the action of the protein kinase A inhibitor H-89

机译：人淋巴细胞中环磷酰胺增强剂对毒胡萝卜素诱导的钙动员的调节对蛋白激酶A抑制剂H-89的作用不敏感

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Ca2+ mobilisation from internal stores and from the extracellular medium is one of the primary events involved in lymphocyte activation and proliferation. Regulation of these processes by adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-dependent protein kinase (PKA) was studied in Fura2-loaded human peripheral blood lymphocytes. Cytosolic Ca2+ concentration ([Ca2+ ](i)) was measured in single cells by the use of a ratio imaging fluorescence microscope and Ca2+ mobilisation was achieved by the use of the endoplasmic reticulum (ER) Ca2+ ATPase inhibitor, thapsigargin (Thg). Our results show that both activation and inhibition of PKA, with forskolin (FSK) and N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide . 2HCl (H-89), respectively, inhibited the Thg-induced Ca2+ entry. Furthermore, FSK also reduced the ability of Thg to release Ca2+ from internal stores. This reduction was inhibited by the adenylyl cyclase (AC) inhibitor 9-(tetrahydro-2-furanyl)-9-H-purin-6-amine (SQ22,536), but not by the PKA inhibitor H89, indicating that cAMP but not PKA is responsible for this effect. FSK effect was mimicked by dibutyryl cAMP (dbcAMP) and by inhibition of phosphodiesterases (PDEs) with rolipram (ROL) and milrinone (MIL). We also showed that a very high concentration of H-89 (100 muM) releases Ca2+ from an intracellular pool, although this action is probably independent of PKA inhibition. Neither 10 muM H-89 nor other cAMP/PKA-modulating drugs had any effect on the basal [Ca2+](i) of human lymphocytes. We conclude that PKA may act as a fine modulator of capacitative Ca2+ entry, while cAMP has a PKA-independent interaction with the Ca2+ stores of human lymphocytes. (C) 2001 Elsevier Science Inc. All rights reserved. [References: 32]
机译：从内部存储和细胞外介质中动员的Ca2 +是涉及淋巴细胞激活和增殖的主要事件之一。在负载Fura2的人外周血淋巴细胞中研究了腺苷3'，5'-环一磷酸（cAMP）和cAMP依赖性蛋白激酶（PKA）对这些过程的调节。使用比率成像荧光显微镜测量单个细胞中的胞质Ca2 +浓度（[Ca2 +]（i）），并使用内质网（ER）Ca2 + ATPase抑制剂thapsigargin（Thg）实现Ca2 +动员。我们的结果表明，福斯科林（FSK）和N- [2-（对溴肉桂酸氨基）乙基] -5-异喹啉磺酰胺对PKA的激活和抑制作用。 2HCl（H-89）分别抑制Thg诱导的Ca2 +进入。此外，FSK还降低了Thg从内部存储中释放Ca2 +的能力。该降低受到腺苷酸环化酶（AC）抑制剂9-（四氢-2-呋喃基）-9-H-嘌呤-6-胺（SQ22,536）的抑制，但不受PKA抑制剂H89的抑制，表明cAMP但不是PKA负责此效果。 FSK的作用可通过二丁酰cAMP（dbcAMP）以及通过咯利普兰（ROL）和米力农（MIL）抑制磷酸二酯酶（PDE）来模拟。我们还显示了很高浓度的H-89（100μM）从细胞内池中释放Ca2 +，尽管这种作用可能与PKA抑制无关。 10μMH-89或其他cAMP / PKA调节药物均未对人淋巴细胞的基础[Ca2 +]（i）产生任何影响。我们得出的结论是，PKA可以充当电容性Ca2 +进入的精细调节剂，而cAMP具有与人类淋巴细胞Ca2 +储存区无关的PKA相互作用。 （C）2001 Elsevier Science Inc.保留所有权利。 [参考：32]

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