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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1143911
- author
- Nilsson, David
LU
; Wackenfors, Angelica
LU
; Gustafsson, Lotta
LU
; Ugander, Martin
LU
; Ingemansson, Richard
LU
; Edvinsson, Lars
LU
and Malmsjö, Malin
LU
- organization
- publishing date
- 2008
- 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
- pmid:18031734
- 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
- 2016-04-01 12:04:15
- date last changed
- 2024-01-08 07:15:27
@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}},
keywords = {{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}},
doi = {{10.1016/j.ejphar.2007.10.071}},
volume = {{580}},
year = {{2008}},
}