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Importance of ERK1/2 in upregulation of endothelin type B receptors in cerebral arteries

Henriksson, Marie LU ; Xu, Cang-Bao LU and Edvinsson, Lars LU (2004) In British Journal of Pharmacology 142(7). p.1155-1161
Abstract
1 This study examines the importance of mitogen-activated protein kinases (MAPKs) in upregulation of endothelin type B (ETB) receptors. 2 Rat middle cerebral arteries (MCAs) were incubated for 24 h with or without kinase inhibitors. Vessel segments were mounted in myographs and the contractile responses to endothelin-1 (ET-1; ETA and ETB receptor agonist) and sarafotoxin 6c (S6c; ETB receptor agonist) were studied. We used real-time PCR to measure the receptor mRNA levels. An ELISA assay showed the activation of ERK1/2 kinases after 3 h. Immunohistochemistry revealed the presence of ETB receptors on the vessels. 3 After organ culture, S6c induced vasoconstriction. Incubation with the MEK/ERK inhibitors U0126 and SB386023 diminished the... (More)
1 This study examines the importance of mitogen-activated protein kinases (MAPKs) in upregulation of endothelin type B (ETB) receptors. 2 Rat middle cerebral arteries (MCAs) were incubated for 24 h with or without kinase inhibitors. Vessel segments were mounted in myographs and the contractile responses to endothelin-1 (ET-1; ETA and ETB receptor agonist) and sarafotoxin 6c (S6c; ETB receptor agonist) were studied. We used real-time PCR to measure the receptor mRNA levels. An ELISA assay showed the activation of ERK1/2 kinases after 3 h. Immunohistochemistry revealed the presence of ETB receptors on the vessels. 3 After organ culture, S6c induced vasoconstriction. Incubation with the MEK/ERK inhibitors U0126 and SB386023 diminished the contractile response to S6c. The p38 MAPK inhibitor SB239063 did not affect the S6c-induced contraction. 4 The ET-1-induced vasoconstriction was increased after incubation with SB386023 or SB239063, while unaffected by U0126. 5 The ETB receptor mRNA levels were diminished by SB386023 and U0126. The ETA receptor mRNA levels were unaffected. 6 The levels of activated ERK1/2 kinases were significantly higher after 3 h of organ culture as compared to fresh vessels. 7 The level of ETB receptor protein on the smooth muscle cells of the MCA, visualised by immunohistochemistry, was somewhat diminished by SB386023. 8 Our results show that the ERK1/2 MAPK is important in the upregulation of contractile ETB receptors in MCA after organ culture. Since there is a similar upregulation in models of focal ischaemia and subarachnoid haemorrhage, this may be an important pathophysiological event. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
MAPK, upregulation, endothelin, ETB receptor, MCA, ERK1/2
in
British Journal of Pharmacology
volume
142
issue
7
pages
1155 - 1161
publisher
The British Pharmacological Society
external identifiers
  • wos:000223201500014
  • pmid:15237095
  • scopus:4143053531
ISSN
1476-5381
DOI
10.1038/sj.bjp.0705803
language
English
LU publication?
yes
id
7f2b4375-ba68-4bac-92f5-32d6fe95e68b (old id 270954)
date added to LUP
2007-10-30 09:39:43
date last changed
2017-01-01 07:05:49
@article{7f2b4375-ba68-4bac-92f5-32d6fe95e68b,
  abstract     = {1 This study examines the importance of mitogen-activated protein kinases (MAPKs) in upregulation of endothelin type B (ETB) receptors. 2 Rat middle cerebral arteries (MCAs) were incubated for 24 h with or without kinase inhibitors. Vessel segments were mounted in myographs and the contractile responses to endothelin-1 (ET-1; ETA and ETB receptor agonist) and sarafotoxin 6c (S6c; ETB receptor agonist) were studied. We used real-time PCR to measure the receptor mRNA levels. An ELISA assay showed the activation of ERK1/2 kinases after 3 h. Immunohistochemistry revealed the presence of ETB receptors on the vessels. 3 After organ culture, S6c induced vasoconstriction. Incubation with the MEK/ERK inhibitors U0126 and SB386023 diminished the contractile response to S6c. The p38 MAPK inhibitor SB239063 did not affect the S6c-induced contraction. 4 The ET-1-induced vasoconstriction was increased after incubation with SB386023 or SB239063, while unaffected by U0126. 5 The ETB receptor mRNA levels were diminished by SB386023 and U0126. The ETA receptor mRNA levels were unaffected. 6 The levels of activated ERK1/2 kinases were significantly higher after 3 h of organ culture as compared to fresh vessels. 7 The level of ETB receptor protein on the smooth muscle cells of the MCA, visualised by immunohistochemistry, was somewhat diminished by SB386023. 8 Our results show that the ERK1/2 MAPK is important in the upregulation of contractile ETB receptors in MCA after organ culture. Since there is a similar upregulation in models of focal ischaemia and subarachnoid haemorrhage, this may be an important pathophysiological event.},
  author       = {Henriksson, Marie and Xu, Cang-Bao and Edvinsson, Lars},
  issn         = {1476-5381},
  keyword      = {MAPK,upregulation,endothelin,ETB receptor,MCA,ERK1/2},
  language     = {eng},
  number       = {7},
  pages        = {1155--1161},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Importance of ERK1/2 in upregulation of endothelin type B receptors in cerebral arteries},
  url          = {http://dx.doi.org/10.1038/sj.bjp.0705803},
  volume       = {142},
  year         = {2004},
}