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Professor Malin Malmsjö, MD, PhD. Photo.

Malin Malmsjö

Professor

Professor Malin Malmsjö, MD, PhD. Photo.

PKC and MAPK signalling pathways regulate vascular endothelin receptor expression

Author

  • David Nilsson
  • Angelica Wackenfors
  • Lotta Gustafsson
  • Martin Ugander
  • Richard Ingemansson
  • Lars Edvinsson
  • Malin Malmsjö

Summary, in English

Up-regulation of vascular endothelin type A (ET(A)) and type B (ET(B)) receptors are implicated in the pathogenesis of cardiovascular disease. Culture of arteries has been shown to induce similar receptor alterations and has therefore been suggested as a suitable method for in detail delineation of the regulation of endothelin receptors. We hypothesize that protein kinase C (PKC) and mitogen-activated kinases (MAPK) are involved in the regulation of endothelin receptors. Porcine coronary arteries were studied before and after 24 h of culture, using in vitro pharmacology, real-time PCR and immunofluorescence techniques. Sarafotoxin 6c and endothelin ET-1 were used to examine the endothelin ET(A) and ET(B) receptor effects. The involvement of PKC and MAPK in the receptor regulation was examined by culture in the presence of antagonists. Organ culture resulted in increased sarafotoxin 6c and endothelin-1 contractions, endothelin ET(A) and ET(B) receptor immunofluorescence staining intensities and endothelin ET(B), but not ET(A), receptor mRNA levels. The general PKC inhibitors, bisindolylmaleimide I (10 muM) or Ro-32-0432 (10 muM), inhibited these effects. Also, the increase in sarafotoxin 6c contraction, endothelin ET(B) receptor and mRNA levels and endothelin ET(A) and ET(B) immunofluorescence staining intensities were inhibited by MAPK inhibitors for extracellular signal related kinases 1 and 2 (ERK1/2), PD98059 (10 muM), C-jun terminal kinase (JNK), SP600125 (10 muM), but not by p38 MAPK, SB203580 (10 muM). In conclusion, PKC and MAPK seem to be involved in the regulation of endothelin receptor expression in porcine coronary arteries. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the development of vascular endothelin receptor changes in cardiovascular disease.

Department/s

  • Medicine/Emergency Medicine, Lund
  • Division of Microbiology, Immunology and Glycobiology - MIG
  • Ophthalmology, Lund
  • Clinical Physiology (Lund)
  • Thoracic Surgery

Publishing year

2008

Language

English

Pages

190-200

Publication/Series

European Journal of Pharmacology

Volume

580

Issue

1-2

Document type

Journal article

Publisher

Elsevier

Topic

  • Pharmacology and Toxicology

Keywords

  • Endothelin
  • Coronary artery
  • Contraction
  • Vascular

Status

Published

ISBN/ISSN/Other

  • ISSN: 1879-0712