Up-regulation of endothelin receptor function and mRNA expression in airway smooth muscle cells following Sephadex-induced airway inflammation

Bengt W Granström, Cang-Bao Xu, Elisabet Nilsson, Ursula Hultkvist Bengtsson, Lars Edvinsson

12 Citations (Scopus)

Abstract

The hypothesis that up-regulation of bronchial constrictor endothelin receptors in airway smooth muscle cells may contribute to hyperreactivity during airway inflammation was tested in the present study by quantitative endothelin receptor mRNA analysis and functional responses in ring segments of rat trachea and bronchi. Real time reverse transcription polymerase chain reaction was used to quantify endothelin receptor expression in rat airway smooth muscle cells following Sephadex-induced inflammation. Compared with controls, Sephadex-induced airway inflammation caused a significant increase (3.9 times P<0.05) of endothelin receptor type B mRNA expression in bronchial smooth muscle cells, but not in tracheal smooth muscle cells. Functional myograph studies of bronchial and tracheal ring segments without epithelium (mechanically denuded) revealed an increase of the maximum contractile effects of endothelin-1 (a dual agonist for both endothelin type A and B receptors) and sarafotoxin 6c (a selective agonist for endothelin B receptors) in bronchial smooth muscle cells in Sephadex-induced inflammation, but not in tracheal smooth muscle cells. The enhanced maximal responses of bronchial smooth muscle cells to endothelin-1 and sarafotoxin 6c in Sephadex-induced inflammation support our molecular findings and hence imply a role for endothelin B receptors in airway hyperreactivity during airway inflammation.

Original languageEnglish
JournalBasic & clinical pharmacology & toxicology
Volume95
Issue number1
Pages (from-to)43-8
Number of pages6
ISSN1742-7835
DOIs
Publication statusPublished - Jul 2004
Externally publishedYes

Keywords

  • Animals
  • Bronchi
  • Dextrans
  • Endothelin-1
  • In Vitro Techniques
  • Inflammation
  • Male
  • Myocytes, Smooth Muscle
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trachea
  • Up-Regulation
  • Viper Venoms

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