Importance of ERK1/2 in upregulation of endothelin type B receptors in cerebral arteries
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/270954
- author
- Henriksson, Marie LU ; Xu, Cang-Bao LU and Edvinsson, Lars LU
- organization
- publishing date
- 2004
- 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
- Wiley
- 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
- 2016-04-01 16:27:25
- date last changed
- 2024-01-11 08:24:30
@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}},
keywords = {{MAPK; upregulation; endothelin; ETB receptor; MCA; ERK1/2}},
language = {{eng}},
number = {{7}},
pages = {{1155--1161}},
publisher = {{Wiley}},
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}},
doi = {{10.1038/sj.bjp.0705803}},
volume = {{142}},
year = {{2004}},
}