Store-operated calcium entry in vascular endothelial cells is inhibited by cGMP via a protein kinase G-dependent mechanism.
Store-operated Ca(2+) entry in vascular endothelial cells not only serves to refill the intracellular Ca(2+) 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 Ca(2+) entry in aortic endothelial cells. Cyclopiazonic acid (CPA) and thapsigargin, two selective inhibitors of endoplasmic reticulum Ca(2+)-ATPase, were used to induce store-operated Ca(2+) entry. 8-Bromo-cGMP, an activator of protein kinase G, inhibited the CPA- or thapsigargin-induced Ca(2+) entry in a concentration-dependent manner. An inhibitor of protein kinase G, KT5823 (1 microM) or H-8 (10 microM), abolished the inhibitory action of 8-bromo-cGMP and resumed Ca(2+) 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 Ca(2+) influx due to CPA. Patch clamp study confirmed the existence of a CPA-activated Ca(2+)-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 Ca(2+) entry in vascular endothelial cells.
Kwan
H Y
HY
Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China.
Huang
Y
Y
Yao
X
X
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases; D004730:Endothelium, Vascular / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007211:Indoles; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D011494:Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D002118:Calcium; C000543:cyclopiazonic acid