NDLI: Store-operated Calcium Entry in Vascular Endothelial Cells Is Inhibited by cGMP via a Protein Kinase G-dependent Mechanism

Content Provider	Journal of Biological Chemistry (JBC)
Author	Kwan, Hiu-Yee Huang, Yu Yao, Xiaoqiang
Abstract	Store-operated Ca2+ entry in vascular endothelial cells not only serves to refill the intracellular Ca2+ stores, but also acts to stimulate the synthesis of nitric oxide, a key vasodilatory factor. In this study, we examined the role of cGMP in regulating the store-operated Ca2+ entry in aortic endothelial cells. Cyclopiazonic acid (CPA) and thapsigargin, two selective inhibitors of endoplasmic reticulum Ca2+-ATPase, were used to induce store-operated Ca2+ entry. 8-Bromo-cGMP, an activator of protein kinase G, inhibited the CPA- or thapsigargin-induced Ca2+ entry in a concentration-dependent manner. An inhibitor of protein kinase G, KT5823 (1 μm) or H-8 (10 μm), abolished the inhibitory action of 8-bromo-cGMP and resumed Ca2+ entry. Addition ofS-nitroso-N-acetylpenicillamine (a nitric oxide donor) or dipyridamole (a cGMP phosphodiesterase inhibitor) during CPA treatment elevated cellular cGMP levels, stimulated protein kinase G activity, and at the same time reduced Ca2+ influx due to CPA. Patch clamp study confirmed the existence of a CPA-activated Ca2+-permeable channel sensitive to cGMP inhibition. These results suggest that cGMP via a protein kinase G-dependent mechanism may play a key role in the regulation of the store-operated Ca2+ entry in vascular endothelial cells.
Related Links	http://www.jbc.org/content/275/10/6758.abstract
Ending Page	6763
Starting Page	6758
Page Count	6
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	10
Volume Number	275
DOI	10.1074/jbc.275.10.6758
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2000-03-10
Access Restriction	Open
Subject Keyword	Cytoplasmic free calcium concentration ([Ca2+]i) Protein kinase G (PKG) Bromo (Br) Cyclopiazonic acid (CPA) Phosphate-buffered saline (PBS) Normal physiological saline solution (N-PSS) Calcium-free physiological saline solution (0Ca2+-PSS) S-nitroso-N-acetylpenicillamine (SNAP) MECHANISMS OF SIGNAL TRANSDUCTION
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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