Human cerebrovascular contractile receptors are upregulated via a B-Raf/MEK/ERK-sensitive signaling pathway |
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Authors: | Hilda Ahnstedt Hans Säveland Ola Nilsson Lars Edvinsson |
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Institution: | (1) Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, Lund, Sweden;(2) Department of Neurosurgery, Lund University Hospital, Lund, Sweden |
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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. |
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