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Propofol inhibits expression of angiotensin II receptor type 2 in dorsal root ganglion neurons

The renin-angiotensin system (RAS) is involved in nociception and has functions in the cardiovascular system. The primary role of the RAS is to mediate the effect of angiotensin II (Ang II) through Ang II receptor type 2 (AT2). Due to this, AT2 has become a novel therapeutic target for the relief of...

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Autores principales: Pan, Bingbing, Cheng, Zhigang, Kong, Gaoyin, Song, Zongbin, Wang, Yunjiao, Wei, Lai, Xiao, Dan, Zhao, Yuan, Guo, Qulian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403460/
https://www.ncbi.nlm.nih.gov/pubmed/28450911
http://dx.doi.org/10.3892/etm.2017.4040
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author Pan, Bingbing
Cheng, Zhigang
Kong, Gaoyin
Song, Zongbin
Wang, Yunjiao
Wei, Lai
Xiao, Dan
Zhao, Yuan
Guo, Qulian
author_facet Pan, Bingbing
Cheng, Zhigang
Kong, Gaoyin
Song, Zongbin
Wang, Yunjiao
Wei, Lai
Xiao, Dan
Zhao, Yuan
Guo, Qulian
author_sort Pan, Bingbing
collection PubMed
description The renin-angiotensin system (RAS) is involved in nociception and has functions in the cardiovascular system. The primary role of the RAS is to mediate the effect of angiotensin II (Ang II) through Ang II receptor type 2 (AT2). Due to this, AT2 has become a novel therapeutic target for the relief of peripheral neuropathic pain in humans. As it is one of the most popular induction agents of general anesthesia, propofol also exerts peripheral antinociceptive effects. The present study assessed the effect of propofol on the expression of AT2 in cultured dorsal root ganglion (DRG) neurons. The results indicate that propofol decreases AT2 mRNA expression in a statistically significant dose- and time-dependent manner (P<0.05). This resulted in a marked decrease in AT2 protein expression and the density of Ang II-binding AT2 on the cell membrane of DRG neurons. The effect of propofol was reversed by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Although propofol exhibited no significant effect on AT2 gene promoter activity, it significantly decreased the stability of AT2 mRNA (P<0.05). However, this effect was reversed by LY294002. In addition, propofol increased PI3K activity in a concentration-dependent manner in DRG neurons. In conclusion, to the best of our knowledge, the current study provides the first evidence suggesting that propofol inhibits the expression of AT2 in DRG neurons by decreasing the stability of AT2 mRNA through a PI3K-dependent mechanism. The present study provides novel insights into the mechanisms of the peripheral antinociceptive action of propofol and suggests a potential means of regulating Ang II/AT2 signaling in the peripheral nervous system.
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spelling pubmed-54034602017-04-27 Propofol inhibits expression of angiotensin II receptor type 2 in dorsal root ganglion neurons Pan, Bingbing Cheng, Zhigang Kong, Gaoyin Song, Zongbin Wang, Yunjiao Wei, Lai Xiao, Dan Zhao, Yuan Guo, Qulian Exp Ther Med Articles The renin-angiotensin system (RAS) is involved in nociception and has functions in the cardiovascular system. The primary role of the RAS is to mediate the effect of angiotensin II (Ang II) through Ang II receptor type 2 (AT2). Due to this, AT2 has become a novel therapeutic target for the relief of peripheral neuropathic pain in humans. As it is one of the most popular induction agents of general anesthesia, propofol also exerts peripheral antinociceptive effects. The present study assessed the effect of propofol on the expression of AT2 in cultured dorsal root ganglion (DRG) neurons. The results indicate that propofol decreases AT2 mRNA expression in a statistically significant dose- and time-dependent manner (P<0.05). This resulted in a marked decrease in AT2 protein expression and the density of Ang II-binding AT2 on the cell membrane of DRG neurons. The effect of propofol was reversed by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Although propofol exhibited no significant effect on AT2 gene promoter activity, it significantly decreased the stability of AT2 mRNA (P<0.05). However, this effect was reversed by LY294002. In addition, propofol increased PI3K activity in a concentration-dependent manner in DRG neurons. In conclusion, to the best of our knowledge, the current study provides the first evidence suggesting that propofol inhibits the expression of AT2 in DRG neurons by decreasing the stability of AT2 mRNA through a PI3K-dependent mechanism. The present study provides novel insights into the mechanisms of the peripheral antinociceptive action of propofol and suggests a potential means of regulating Ang II/AT2 signaling in the peripheral nervous system. D.A. Spandidos 2017-03 2017-01-12 /pmc/articles/PMC5403460/ /pubmed/28450911 http://dx.doi.org/10.3892/etm.2017.4040 Text en Copyright: © Pan et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Pan, Bingbing
Cheng, Zhigang
Kong, Gaoyin
Song, Zongbin
Wang, Yunjiao
Wei, Lai
Xiao, Dan
Zhao, Yuan
Guo, Qulian
Propofol inhibits expression of angiotensin II receptor type 2 in dorsal root ganglion neurons
title Propofol inhibits expression of angiotensin II receptor type 2 in dorsal root ganglion neurons
title_full Propofol inhibits expression of angiotensin II receptor type 2 in dorsal root ganglion neurons
title_fullStr Propofol inhibits expression of angiotensin II receptor type 2 in dorsal root ganglion neurons
title_full_unstemmed Propofol inhibits expression of angiotensin II receptor type 2 in dorsal root ganglion neurons
title_short Propofol inhibits expression of angiotensin II receptor type 2 in dorsal root ganglion neurons
title_sort propofol inhibits expression of angiotensin ii receptor type 2 in dorsal root ganglion neurons
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403460/
https://www.ncbi.nlm.nih.gov/pubmed/28450911
http://dx.doi.org/10.3892/etm.2017.4040
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