Comparison of the Effects of Endothelin-1, -2 and -3 (1-31) on Changes in [Ca^<2+>]_i in Human Coronary Artery Smooth Muscle Cells

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Author(s)

Abstract

We have previously found that human chymase selectively cleaves big endothelins (ETs) at the Tyr<SUP>31</SUP>-Gly<SUP>32</SUP> bond to produce 31-amino-acid endothelins, ETs (1 - 31). In the present study, we investigated the effects of ETs (1 - 31) on changes in intracellular free Ca<SUP>2+</SUP> ([Ca<SUP>2+</SUP>]<SUB>i</SUB>) in cultured human coronary artery smooth muscle cells (HCASMCs) using confocal laser microscopy. ETs (1 - 31) increased [Ca<SUP>2+</SUP>]<SUB>i</SUB> in a concentration-dependent manner. Phosphoramidon did not inhibit the increases in [Ca<SUP>2+</SUP>]<SUB>i</SUB> caused by ETs (1 - 31). The [Ca<SUP>2+</SUP>]<SUB>i</SUB> increases induced by ETs (1 - 31) were compared to those of ETs (1 - 21) and big ETs. ET-1 (1 - 21) was about 10-times more potent than big ET-1 or ET-1 (1 - 31), whereas big ET-2 was 10-times less potent than ET-2 (1 - 21) or ET-2 (1 - 31). ETs (1 - 31) may induce [Ca<SUP>2+</SUP>]<SUB>i</SUB> increase through ET<SUB>A</SUB>-type or ET<SUB>A</SUB>-type-like receptors. The 10<SUP>-12</SUP> M ET (1 - 31)-induced increases in [Ca<SUP>2+</SUP>]<SUB>i</SUB> were not affected by removal of extracellular Ca<SUP>2+</SUP>, but were inhibited by thapsigargin. These results suggested that ET-1, -2 and -3 (1 - 31) showed similar potencies in increasing [Ca<SUP>2+</SUP>]<SUB>i</SUB> and mechanisms of ET (1 - 31)-induced increases in [Ca<SUP>2+</SUP>]<SUB>i</SUB> may be similar among the three ETs (1 - 31).

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 81(3), 298-304, 1999-11

    The Japanese Pharmacological Society

References:  27

Codes

  • NII Article ID (NAID)
    10008197322
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4918367
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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