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PKC and MAPK signalling pathways regulate vascular endothelin receptor expression

Nilsson, David LU ; Wackenfors, Angelica LU ; Gustafsson, Lotta LU ; Ugander, Martin LU ; Ingemansson, Richard LU ; Edvinsson, Lars LU and Malmsjö, Malin LU (2008) In European Journal of Pharmacology 580(1-2). p.190-200
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Endothelin, Coronary artery, Contraction, Vascular
in
European Journal of Pharmacology
volume
580
issue
1-2
pages
190 - 200
publisher
Elsevier
external identifiers
  • pmid:18031734
  • wos:000252983100025
  • scopus:37649008331
ISSN
1879-0712
DOI
10.1016/j.ejphar.2007.10.071
language
English
LU publication?
yes
id
4c95b520-8282-40ce-be10-51b1110340d5 (old id 1143911)
date added to LUP
2008-08-15 09:04:50
date last changed
2017-01-01 04:48:30
@article{4c95b520-8282-40ce-be10-51b1110340d5,
  abstract     = {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.},
  author       = {Nilsson, David and Wackenfors, Angelica and Gustafsson, Lotta and Ugander, Martin and Ingemansson, Richard and Edvinsson, Lars and Malmsjö, Malin},
  issn         = {1879-0712},
  keyword      = {Endothelin,Coronary artery,Contraction,Vascular},
  language     = {eng},
  number       = {1-2},
  pages        = {190--200},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {PKC and MAPK signalling pathways regulate vascular endothelin receptor expression},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2007.10.071},
  volume       = {580},
  year         = {2008},
}