Human cerebrovascular contractile receptors are upregulated via a B-Raf/MEK/ERK-sensitive signaling pathway.
(2011) In BMC Neuroscience 12.- Abstract
- ABSTRACT:
BACKGROUND: Cerebral ischemia results in a rapid increase in contractile cerebrovascular receptors, such as the 5-hydroxytryptamine type 1B (5-HT1B), angiotensin II type 1 (AT1), and endothelin type B (ETB) receptors, in the vessel walls within the ischemic region, which further impairs local blood flow and aggravates tissue damage. This receptor upregulation occurs via activation of the mitogen-activated protein kinase pathway. We therefore hypothesized an important role for B-Raf, the first signaling molecule in the pathway. To test our hypothesis, human cerebral arteries were incubated at 37°C for 48 h in the absence or presence of a B-Raf inhibitor: SB-386023 or SB-590885. Contractile properties were evaluated in a... (More) - ABSTRACT:
BACKGROUND: Cerebral ischemia results in a rapid increase in contractile cerebrovascular receptors, such as the 5-hydroxytryptamine type 1B (5-HT1B), angiotensin II type 1 (AT1), and endothelin type B (ETB) receptors, in the vessel walls within the ischemic region, which further impairs local blood flow and aggravates tissue damage. This receptor upregulation occurs via activation of the mitogen-activated protein kinase pathway. We therefore hypothesized an important role for B-Raf, the first signaling molecule in the pathway. To test our hypothesis, human cerebral arteries were incubated at 37°C for 48 h in the absence or presence of a B-Raf inhibitor: SB-386023 or SB-590885. Contractile properties were evaluated in a myograph and protein expression of the individual receptors and activated phosphorylated B-Raf (p-B-Raf) was evaluated immunohistochemically.
RESULTS: 5-HT1B, AT1, and ETB receptor-mediated contractions were significantly reduced by application of SB-590885, and to a smaller extent by SB-386023. A marked reduction in AT1 receptor immunoreactivity was observed after treatment with SB-590885. Treatment with SB-590885 and SB-386023 diminished the culture-induced increase of p-B-Raf immunoreactivity.
CONCLUSIONS: B-Raf signaling has a key function in the altered expression of vascular contractile receptors observed after organ culture. Therefore, specific targeting of B-Raf might be a novel approach to reduce tissue damage after cerebral ischemia by preventing the previously observed upregulation of contractile receptors in smooth muscle cells. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1777596
- author
- Ahnstedt, Hilda LU ; Säveland, Hans LU ; Nilsson, Ola LU and Edvinsson, Lars LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- BMC Neuroscience
- volume
- 12
- article number
- 5
- publisher
- BioMed Central (BMC)
- external identifiers
-
- wos:000286509700001
- pmid:21223556
- scopus:78651076674
- ISSN
- 1471-2202
- DOI
- 10.1186/1471-2202-12-5
- language
- English
- LU publication?
- yes
- id
- d1e7d484-39d9-47f0-86a0-7435710797d5 (old id 1777596)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21223556?dopt=Abstract
- date added to LUP
- 2016-04-04 09:11:43
- date last changed
- 2024-01-27 08:19:57
@article{d1e7d484-39d9-47f0-86a0-7435710797d5,
abstract = {{ABSTRACT:<br/><br>
BACKGROUND: Cerebral ischemia results in a rapid increase in contractile cerebrovascular receptors, such as the 5-hydroxytryptamine type 1B (5-HT1B), angiotensin II type 1 (AT1), and endothelin type B (ETB) receptors, in the vessel walls within the ischemic region, which further impairs local blood flow and aggravates tissue damage. This receptor upregulation occurs via activation of the mitogen-activated protein kinase pathway. We therefore hypothesized an important role for B-Raf, the first signaling molecule in the pathway. To test our hypothesis, human cerebral arteries were incubated at 37°C for 48 h in the absence or presence of a B-Raf inhibitor: SB-386023 or SB-590885. Contractile properties were evaluated in a myograph and protein expression of the individual receptors and activated phosphorylated B-Raf (p-B-Raf) was evaluated immunohistochemically.<br/><br>
<br/><br>
RESULTS: 5-HT1B, AT1, and ETB receptor-mediated contractions were significantly reduced by application of SB-590885, and to a smaller extent by SB-386023. A marked reduction in AT1 receptor immunoreactivity was observed after treatment with SB-590885. Treatment with SB-590885 and SB-386023 diminished the culture-induced increase of p-B-Raf immunoreactivity.<br/><br>
<br/><br>
CONCLUSIONS: B-Raf signaling has a key function in the altered expression of vascular contractile receptors observed after organ culture. Therefore, specific targeting of B-Raf might be a novel approach to reduce tissue damage after cerebral ischemia by preventing the previously observed upregulation of contractile receptors in smooth muscle cells.}},
author = {{Ahnstedt, Hilda and Säveland, Hans and Nilsson, Ola and Edvinsson, Lars}},
issn = {{1471-2202}},
language = {{eng}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Neuroscience}},
title = {{Human cerebrovascular contractile receptors are upregulated via a B-Raf/MEK/ERK-sensitive signaling pathway.}},
url = {{https://lup.lub.lu.se/search/files/5257648/1787086.pdf}},
doi = {{10.1186/1471-2202-12-5}},
volume = {{12}},
year = {{2011}},
}