Store-operated calcium entry in vascular endothelial cells is inhibited by cGMP via a protein kinase G-dependent mechanism

Hiu Yee Kwan, Yu Huang, Xiaoqiang Yao*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

86 Citations (Scopus)

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 ♂) or H-8 (10 μM), abolished the inhibitory action of 8-bromo-cGMP and resumed Ca2+ entry. Addition of S-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.

Original languageEnglish
Pages (from-to)6758-6763
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number10
DOIs
Publication statusPublished - 10 Mar 2000

Scopus Subject Areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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