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2002 Fiscal Year Final Research Report Summary

Relationship between lipid mediator receptors and lipid-induced impairment of human endothelial cells

Research Project

Project/Area Number 13672293
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionNagoya City University

Principal Investigator

MURAKI Katsuhiko  Nagoya City University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究科, 助教授 (20254310)

Project Period (FY) 2001 – 2002
Keywordshuman endothelial cell / lipid mediator / endothelial dysfunction / Ca / cell death
Research Abstract

2001
Ca^<2+> entry pathway activated by sphingosine-1-phosphate (S1P) was examined in human umbilical vein endothelial cells (HUVECs) by measuring intracellular Ca^<2+> concentration ([Ca^<2+>]_i), whole-cell membrane currents and single channel activity. Application of S1P to HUVECs induced a slowly developing increase in [Ca^<2+>_i. When Ca^<2+> was absent in the bathing solution, S1P did not affect [Ca^<2+>]_i Addition of Ca^<2+> to the bathing solution, however, produced a sustained increase in [Ca^<2+>_i in the presence of S1P, suggesting that influx of Ca^<2+> plays an obligatory role in elevation of [Ca^<2+>_i by S1P. Pretreatment of HUVECs with pertussis toxin (PTX) abolished S1P-induced elevation of [Ca^<2+>]_i. When whole-cell membrane currents were recorded under the monitoring of [Ca^<2+>]_i, the application of S1P induced a tiny inward current (I_<S1P>) which was followed by the elevation of [Ca^<2+>]_i. The reversal potential of I_<S1P> revealed that I_<S1P> is a ***-selec … More tive cation (NSC) current. When S1P was included in the pipette solution in the excised inside-out patch clamp configuration, ***gle channel with a conductance of 17 pS was activated, depending on the presence of intracellular GTP. These results suggest that S1P has a novel function to activate a NSC-channel in a GTP-dependent manner via a PTX-sensitive G-protein. The NSC-channel activated by S1P acts as a Ca^<2+> entry pathway in endothelium and may regulate the cell-proliferation. These results have been published in J. Physiol. (537, 431-441, 2001)
2002
Effects of palmitoylcarnitine (palcar), a lipid that is released from various types of cells under the ischemic conditions, on [Ca^<2+>]_i were examined in HUVECs and compared with those of S1P. Application of palcar elevated [Ca^<2+>]_i in HUVECs and its potency was about 30 times lower than that of S1P. Response to 3 μM palcar in each HUVEC clearly paralleled that to 0.3 μM S1P. In addition, HUVECs that were treated with PTX failed to respond to palcar as werll as to S1P. These results suggest that palcar has a novel action on huvecs as a potential agonist of receptors for S1P. These results have been published in J. Pharmacol. Sci. (in press, 2003) Less

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] K.Muraki, Y.Imaizumi: "A novel action of palmitoyl-L-carnitine in human vascular endothelial cell"Journal of Pharmacological Sciences. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Imaizumi et al.: "Molecular basis of pimaran compounds as novel activators of large conductance Ca^<2+>activated K^+ channel α-subunit"Molecular Pharmacology. 62. 836-846 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Ohya et al.: "Molecular and functional characterization of ERG, KCNQ and KCNE subtypes in rat stomach smooth muscle"American Journal of Physiology. 282. G277-G287 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Petrova et al.: "Advanced glycation endproduct-induced calcium handling impairment in mouse cardiac myocytes"American Journal of Molecular and Cellular Cardiology. 34. 1425-1431 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamura et al.: "Mechanisms underlying the activation of large conductance Ca^<2+> activated K^+ channels by nordihydroguaiaretic acid"Japanese Journal of Pharmacology. 89. 53-63 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Muraki, Y.Imaizumi: "A novel function of sphingosine-1-phosphate to activate a non-selective cation channel in human endothelial cells"Journal of Physiology. (London). 537. 431-441 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 村木克彦, 今泉祐冶(分担): "医学のあゆみ-イオンチャネルの最前線、血管平滑筋細胞イオンチャネルとリモデリング"医歯薬出版. 280 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Muraki & Y. Imaizum: "A novel action of palmitoyl-L-carnitine in human vascular endothelial cell"Journal of Pharmacological Sciences. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Imaizumi et al.: "Molecular basis of pimaran compounds as novel activators of large conductance Ca^<2+> activated K^+ channel α-subunit"Molecular Pharmacology. 62. 836-846 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Ohya et al.: "Molecular and functional characterization of ERG, KCNQ and KCNE subtypes in rat stomach smooth muscle"American Journal of Physiology. 282. G277-G287 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Petrova et al.: "Advanced glycation endproduct-induced calcium handling impairment in mouse cardiac myocytes"American Journal of Molecular and Cellular Cardiology. 34. 1425-1431 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamura et al.: "Mechanisms underlying the activation of large conductance Ca^<2+> activated K^+ channels by nordihydroguaiaretic acid"Japanese Journal of Pharmacology. 89. 53-63 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Muraki & Y. Imaizumi: "A novel function of sphingosine-1-phosphate to activate a non-selective cation channel in human endothelial cells"Journal of Physiology. 537. 431-441 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Ohi, et al.: "Local Ca^<2+> transients and distribution of BK channels and ryanodine receptors in smooth muscle cells of guinea pig vas deferens and urinary bladder"Journal of Physiology. 534. 313-326 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Yamada et al.: "Usefulness and limitation of DiBAC_4(3), a voltage-sensitive fluorescent dye, for the measurement of membrane potentials regulated by recombinant large conductance Ca^<2+>-activated K^+ channels in HEK293 cells"Japanese Journal of Pharmacology. 86. 342-350 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Ohi, et al.: "Ca^<2+>-images of smooth muscle cells and endothelial cells in one confocal plane in femoral artery segments of the rat"Japanese Journal of Pharmacology. 85. 106-113 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Ohya et al.: "Molecular cloning and expression of the novel splice variants of K^+ channel-interacting protein 2"Biochemical Biophysical Research Communications. 282. 96-102 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Muraki et al.: "Effects of KRN2391 on membrane currents in rabbit femoral arterial myocytes"British Journal of Pharmacology. 132. 1154-1160 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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