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Vascular endothelin ET(B) receptor-mediated contraction requires phosphorylation of ERK1/2 proteins

Guogang Luo, Roya Jamali, Yong-Xiao Cao, Lars Edvinsson, Cang-Bao Xu

27 Citations (Scopus)

Abstract

In cardiovascular diseases, endothelin type B (ET(B)) receptors in arterial smooth muscle cells are upregulated. The present study revealed that organ culture of rat mesenteric artery segments enhanced endothelin ET(B) receptor-mediated contraction paralleled with increase in the receptor mRNA and protein expressions. The endothelin ET(B) receptor-mediated contraction was associated with increase in phosphorylation of extracellular regulation kinase 1 and 2 (ERK1/2) proteins and elevated levels of intracellular calcium. The elevation curve of intracellular calcium consisted of two phases: one rapid and one sustained. Inhibition of ERK1/2 phosphorylation by SB386023 or blockage of calcium channels by nifedipine significantly reduced the endothelin ET(B) receptor-mediated contraction (P<0.05) and decreased the sustained phase of intracellular calcium level, but not the rapid phase. Thus, phosphorylation of ERK1/2 proteins and elevation of intracellular calcium level are required for endothelin ET(B) receptor-mediated contraction in rat mesenteric artery.

Original languageEnglish
JournalEuropean Journal of Pharmacology
Volume538
Issue number1-3
Pages (from-to)124-31
Number of pages8
ISSN0014-2999
DOIs
Publication statusPublished - 24 May 2006

Keywords

  • Animals
  • Blotting, Western
  • Calcium
  • Calcium Channel Blockers
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors
  • In Vitro Techniques
  • Intracellular Fluid
  • Mesenteric Arteries
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Nifedipine
  • Phosphorylation
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Endothelin B
  • Time Factors
  • Up-Regulation
  • Vasoconstriction
  • Vasoconstrictor Agents
  • Viper Venoms

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