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Inhibition of PKC activity blocks the increase of ET(B )receptor expression in cerebral arteries
BACKGROUND: Previous studies have shown that there is a time-dependent upregulation of contractile endothelin B (ET(B)) receptors in middle cerebral arteries (MCA) after organ culture. This upregulation is dependent on mitogen-activated protein kinases and possibly protein kinase C (PKC). The aim of...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2006
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1698473/ https://www.ncbi.nlm.nih.gov/pubmed/17129394 http://dx.doi.org/10.1186/1471-2210-6-13 |
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author | Henriksson, Marie Vikman, Petter Stenman, Emelie Beg, Saema Edvinsson, Lars |
author_facet | Henriksson, Marie Vikman, Petter Stenman, Emelie Beg, Saema Edvinsson, Lars |
author_sort | Henriksson, Marie |
collection | PubMed |
description | BACKGROUND: Previous studies have shown that there is a time-dependent upregulation of contractile endothelin B (ET(B)) receptors in middle cerebral arteries (MCA) after organ culture. This upregulation is dependent on mitogen-activated protein kinases and possibly protein kinase C (PKC). The aim of this study was to examine the effect of PKC inhibitors with different profiles on the upregulation of contractile ET(B )receptors in rat MCA. Artery segments were incubated for 24 hours at 37°C. To investigate involvement of PKC, inhibitors were added to the medium before incubation. The contractile endothelin-mediated responses were measured and real-time PCR was used to detect endothelin receptor mRNA levels. Furthermore, immunohistochemistry was used to demonstrate the ET(B )receptor protein distribution in the MCA and Western blot to measure which of the PKC subtypes that were affected by the inhibitors. RESULTS: The PKC inhibitors bisindolylmaleimide I, Ro-32-0432 and PKC inhibitor 20–28 attenuated the ET(B )receptor mediated contractions. Furthermore, Ro-32-0432 and bisindolylmaleimide I decreased ET(B )receptor mRNA levels while PKC inhibitor 20–28 reduced the amount of receptor protein on smooth muscle cells. PKC inhibitor 20–28 also decreased the protein levels of the five PKC subtypes studied (α, βI, γ, δ and ε). CONCLUSION: The results show that PKC inhibitors are able to decrease the ET(B )receptor contraction and expression in MCA smooth muscle cells following organ culture. The PKC inhibitor 20–28 affects the protein levels, while Ro-32-0432 and bisindolylmaleimide I affect the mRNA levels, suggesting differences in activity profile. Since ET(B )receptor upregulation is seen in cerebral ischemia, the results of the present study provide a way to interfere with the vascular involvement in cerebral ischemia. |
format | Text |
id | pubmed-1698473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-16984732006-12-13 Inhibition of PKC activity blocks the increase of ET(B )receptor expression in cerebral arteries Henriksson, Marie Vikman, Petter Stenman, Emelie Beg, Saema Edvinsson, Lars BMC Pharmacol Research Article BACKGROUND: Previous studies have shown that there is a time-dependent upregulation of contractile endothelin B (ET(B)) receptors in middle cerebral arteries (MCA) after organ culture. This upregulation is dependent on mitogen-activated protein kinases and possibly protein kinase C (PKC). The aim of this study was to examine the effect of PKC inhibitors with different profiles on the upregulation of contractile ET(B )receptors in rat MCA. Artery segments were incubated for 24 hours at 37°C. To investigate involvement of PKC, inhibitors were added to the medium before incubation. The contractile endothelin-mediated responses were measured and real-time PCR was used to detect endothelin receptor mRNA levels. Furthermore, immunohistochemistry was used to demonstrate the ET(B )receptor protein distribution in the MCA and Western blot to measure which of the PKC subtypes that were affected by the inhibitors. RESULTS: The PKC inhibitors bisindolylmaleimide I, Ro-32-0432 and PKC inhibitor 20–28 attenuated the ET(B )receptor mediated contractions. Furthermore, Ro-32-0432 and bisindolylmaleimide I decreased ET(B )receptor mRNA levels while PKC inhibitor 20–28 reduced the amount of receptor protein on smooth muscle cells. PKC inhibitor 20–28 also decreased the protein levels of the five PKC subtypes studied (α, βI, γ, δ and ε). CONCLUSION: The results show that PKC inhibitors are able to decrease the ET(B )receptor contraction and expression in MCA smooth muscle cells following organ culture. The PKC inhibitor 20–28 affects the protein levels, while Ro-32-0432 and bisindolylmaleimide I affect the mRNA levels, suggesting differences in activity profile. Since ET(B )receptor upregulation is seen in cerebral ischemia, the results of the present study provide a way to interfere with the vascular involvement in cerebral ischemia. BioMed Central 2006-11-28 /pmc/articles/PMC1698473/ /pubmed/17129394 http://dx.doi.org/10.1186/1471-2210-6-13 Text en Copyright © 2006 Henriksson et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Henriksson, Marie Vikman, Petter Stenman, Emelie Beg, Saema Edvinsson, Lars Inhibition of PKC activity blocks the increase of ET(B )receptor expression in cerebral arteries |
title | Inhibition of PKC activity blocks the increase of ET(B )receptor expression in cerebral arteries |
title_full | Inhibition of PKC activity blocks the increase of ET(B )receptor expression in cerebral arteries |
title_fullStr | Inhibition of PKC activity blocks the increase of ET(B )receptor expression in cerebral arteries |
title_full_unstemmed | Inhibition of PKC activity blocks the increase of ET(B )receptor expression in cerebral arteries |
title_short | Inhibition of PKC activity blocks the increase of ET(B )receptor expression in cerebral arteries |
title_sort | inhibition of pkc activity blocks the increase of et(b )receptor expression in cerebral arteries |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1698473/ https://www.ncbi.nlm.nih.gov/pubmed/17129394 http://dx.doi.org/10.1186/1471-2210-6-13 |
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