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Protamine augments stretch induced calcium increase in vascular endothelium
Author(s) -
Murase Kichiro,
Naruse Keiji,
Kimura Akira,
Okumura Kenji,
Hayakawa Tetsuo,
Sokabe Masahiro
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704386
Subject(s) - thapsigargin , umbilical vein , protamine , chemistry , calcium , biophysics , calcium in biology , endothelins , intracellular , endothelium , endocrinology , medicine , microbiology and biotechnology , biochemistry , endothelin receptor , biology , heparin , receptor , in vitro , organic chemistry
Human umbilical vein endothelial cells cultured on a transparent silicone chamber were subjected to a short stretch pulse ( ca . 1 s, 5 – 25% stretch) of their substrate and following increases in intracellular Ca 2+ concentration ([Ca 2+ ] i ) were measured by fluorescence intensity ratiometry using fura‐2. In response to mechanical stretch, the cells in HEPES buffered saline exhibited a Ca 2+ transient in a dose dependent way. The response was completely dependent on external Ca 2+ and inhibited by gadolinium (Gd 3+ ), suggesting that it was mediated by the activation of a stretch activated cation channel (SACatC). Interestingly, the stretch induced Ca 2+ transient was significantly augmented in the presence of basic polypeptide, protamine. This augmented Ca 2+ response was inhibited neither by Gd 3+ nor by the deprivation of external Ca 2+ , indicating that the SACatC is not responsible for this phenomenon. In contrast, this augmentation was inhibited by depletion of intracellular Ca 2+ stores with thapsigargin or by the pretreatment with phospholipase inhibitors such as U73122 and manoalide. These results suggest the presence of a metabotropic mechanoreceptor distinct from the SACatC in vascular endothelium. This augmented [Ca 2+ ] i increase may contribute to the vasodilating response induced by protamine during heparin neutralization in cardiac surgery.British Journal of Pharmacology (2001) 134 , 1403–1410; doi: 10.1038/sj.bjp.0704386