Role of cyclic nucleotides in the control of cytosolic Ca2+ levels in vascular endothelial cells.
1. Endothelial cells have a key role in the cardiovascular system. Most endothelial cell functions depend on changes in cytosolic Ca(2+) concentrations ([Ca(2+)](i)) to some extent and Ca2+ signalling acts to link external stimuli with the synthesis and release of regulatory factors in endothelial cells. The [Ca(2+)](i) is maintained by a well-balanced Ca(2+) flux across the endoplasmic reticulum and plasma membrane. 2. Cyclic nucleotides, such as cAMP and cGMP, are very important second messengers. The cyclic nucleotides can affect [Ca(2+)](i) directly or indirectly (via the actions of protein kinase (PK) A or PKG-mediated phosphorylation) by regulating Ca(2+) mobilization and Ca(2+) influx. Fine-tuning of [Ca(2+)](i) is also fundamental to protect endothelial cells against damaged caused by the excessive accumulation of Ca(2+). 3. Therapeutic agents that control cAMP and cGMP levels have been used to treat various cardiovascular diseases. 4. The aim of the present review is to discuss: (i) the functions of endothelial cells; (ii) the importance of [Ca(2+)](i) in endothelial cells; (iii) the impact of excessive [Ca(2+)](i) in endothelial cells; and (iv) the balanced control of [Ca(2+)](i) in endothelial cells via involvement of cyclic nucleotides (cAMP and cGMP) and their general effectors.
School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China.
H Y
HY
Kwan
Y
Y
Huang
X Q
XQ
Yao
F P
FP
Leung
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D010766:Phosphorylation
D015220:Calcium Channels; D002317:Cardiovascular Agents; D009712:Nucleotides, Cyclic; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D002118:Calcium