Protamine augments stretch induced calcium increase in vascular endothelium

Kichiro Murase, Keiji Naruse, Akira Kimura, Kenji Okumura, Tetsuo Hayakawa, Masahiro Sokabe

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

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 Ca2+ concentration ([Ca2+]i) were measured by fluorescence intensity ratiometry using fura-2. In response to mechanical stretch, the cells in HEPES buffered saline exhibited a Ca2+ transient in a dose dependent way. The response was completely dependent on external Ca2+ and inhibited by gadolinium (Gd3+), suggesting that ir was mediated by the activation of a stretch activated cation channel (SACatC). Interestingly, the stretch induced Ca2+ transient was significantly augmented in the presence of basic polypeptide, protamine. This augmented Ca2+ response was inhibited neither by Gd3+ nor by the deprivation of external Ca2+, indicating that the SACatC is not responsible for this phenomenon. In contrast, this augmentation was inhibited by depletion of intracellular Ca2+ stores with thapsigargin or by the pretreatment with phospholipase inhibitors such as U73122 and manoalide. 5 These results suggest the presence of a metabotropic mechanoreceptor distinct from the SACatC in vascular endothelium. This augmented [Ca2-]i increase may contribute to the vasodilating response induced by protamine during heparin neutralization in cardiac surgery.

Original languageEnglish
Pages (from-to)1403-1410
Number of pages8
JournalBritish Journal of Pharmacology
Volume134
Issue number7
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Pharmacology

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