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  • Nilsson, DavidLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine (author)

PKC and MAPK signalling pathways regulate vascular endothelin receptor expression

  • Article/chapterEnglish2008

Publisher, publication year, extent ...

  • Elsevier BV,2008

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  • LIBRIS-ID:oai:lup.lub.lu.se:4c95b520-8282-40ce-be10-51b1110340d5
  • https://lup.lub.lu.se/record/1143911URI
  • https://doi.org/10.1016/j.ejphar.2007.10.071DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

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  • 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.

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  • Wackenfors, AngelicaLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-awa (author)
  • Gustafsson, LottaLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Oftalmologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Ophthalmology, Lund,Section IV,Department of Clinical Sciences, Lund,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine(Swepub:lu)fysi-lgu (author)
  • Ugander, MartinLund University,Lunds universitet,Klinisk fysiologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Clinical Physiology (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)klfy-mug (author)
  • Ingemansson, RichardLund University,Lunds universitet,Thoraxkirurgi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Thoracic Surgery,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)thor-rin (author)
  • Edvinsson, LarsLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-led (author)
  • Malmsjö, MalinLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Oftalmologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Ophthalmology, Lund,Section IV,Department of Clinical Sciences, Lund(Swepub:lu)med-mma (author)
  • Medicin, LundSektion II (creator_code:org_t)

Related titles

  • In:European Journal of Pharmacology: Elsevier BV580:1-2, s. 190-2001879-07120014-2999

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