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Flucrypyrim, a novel uterine relaxant, has antinociceptive and anti-inflammatory effects in vivo
Consequences of primary dsysmenorrhea (PD) can be severe. Increased prostaglandin production leads to uterine contraction and insufficient blood flow to the endometrium causing ischemia and pain symptoms. Protein tyrosine kinase/phosphatase activities contribute to the modulation of uterine contract...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318994/ https://www.ncbi.nlm.nih.gov/pubmed/28220794 http://dx.doi.org/10.1038/srep42040 |
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author | Li, Zhongtang Wang, Limei Cong, Yue Guo, Lin Lin, Xiaohui Yu, Zuyin Wu, Xingan Dong, Junxing Yang, Rifang Cong, Yuwen |
author_facet | Li, Zhongtang Wang, Limei Cong, Yue Guo, Lin Lin, Xiaohui Yu, Zuyin Wu, Xingan Dong, Junxing Yang, Rifang Cong, Yuwen |
author_sort | Li, Zhongtang |
collection | PubMed |
description | Consequences of primary dsysmenorrhea (PD) can be severe. Increased prostaglandin production leads to uterine contraction and insufficient blood flow to the endometrium causing ischemia and pain symptoms. Protein tyrosine kinase/phosphatase activities contribute to the modulation of uterine contraction. In our previous study, we found the synthetic β-methoxyacrylates compound Fluacrypyrim (FAPM), significantly increased protein tyrosine phosphatases (PTPs) activity, resulting in dephosphorylation of tyrosine kinases. In the present study, we found that FAPM near completely inhibited prostaglandin F2α (PGF(2α))-, oxytocin-, acetylcholine-, and high K(+)-induced uterine contractions in rats in vitro, and decreased rat myometrial myosin light chain (MLC(20)) phosphorylation induced by PGF(2α). A structure–activity relationship assay indicated that the β-methoxyacrylates structure of FAPM is crucial for the inhibition of PGF(2α)-induced uterine contractions. FAPM caused a concentration-dependent parallel rightward shift of the concentration–response curve induced by oxytocin, dose-dependently reduced the number of abdominal constrictions and increased the latency time in PGF(2α)- and acetic acid-induced writhing test in mice in vivo. Furthermore, FAPM considerably inhibited the development of Carr-induced rat paw edemas and thexylene-induced mouse ear edemas. Taken together, our results indicate that FAPM exerts antinociceptive and anti-inflammatory effects in vivo with considerable potential as a novel uterine relaxant. |
format | Online Article Text |
id | pubmed-5318994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53189942017-02-24 Flucrypyrim, a novel uterine relaxant, has antinociceptive and anti-inflammatory effects in vivo Li, Zhongtang Wang, Limei Cong, Yue Guo, Lin Lin, Xiaohui Yu, Zuyin Wu, Xingan Dong, Junxing Yang, Rifang Cong, Yuwen Sci Rep Article Consequences of primary dsysmenorrhea (PD) can be severe. Increased prostaglandin production leads to uterine contraction and insufficient blood flow to the endometrium causing ischemia and pain symptoms. Protein tyrosine kinase/phosphatase activities contribute to the modulation of uterine contraction. In our previous study, we found the synthetic β-methoxyacrylates compound Fluacrypyrim (FAPM), significantly increased protein tyrosine phosphatases (PTPs) activity, resulting in dephosphorylation of tyrosine kinases. In the present study, we found that FAPM near completely inhibited prostaglandin F2α (PGF(2α))-, oxytocin-, acetylcholine-, and high K(+)-induced uterine contractions in rats in vitro, and decreased rat myometrial myosin light chain (MLC(20)) phosphorylation induced by PGF(2α). A structure–activity relationship assay indicated that the β-methoxyacrylates structure of FAPM is crucial for the inhibition of PGF(2α)-induced uterine contractions. FAPM caused a concentration-dependent parallel rightward shift of the concentration–response curve induced by oxytocin, dose-dependently reduced the number of abdominal constrictions and increased the latency time in PGF(2α)- and acetic acid-induced writhing test in mice in vivo. Furthermore, FAPM considerably inhibited the development of Carr-induced rat paw edemas and thexylene-induced mouse ear edemas. Taken together, our results indicate that FAPM exerts antinociceptive and anti-inflammatory effects in vivo with considerable potential as a novel uterine relaxant. Nature Publishing Group 2017-02-21 /pmc/articles/PMC5318994/ /pubmed/28220794 http://dx.doi.org/10.1038/srep42040 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Li, Zhongtang Wang, Limei Cong, Yue Guo, Lin Lin, Xiaohui Yu, Zuyin Wu, Xingan Dong, Junxing Yang, Rifang Cong, Yuwen Flucrypyrim, a novel uterine relaxant, has antinociceptive and anti-inflammatory effects in vivo |
title | Flucrypyrim, a novel uterine relaxant, has antinociceptive and anti-inflammatory effects in vivo |
title_full | Flucrypyrim, a novel uterine relaxant, has antinociceptive and anti-inflammatory effects in vivo |
title_fullStr | Flucrypyrim, a novel uterine relaxant, has antinociceptive and anti-inflammatory effects in vivo |
title_full_unstemmed | Flucrypyrim, a novel uterine relaxant, has antinociceptive and anti-inflammatory effects in vivo |
title_short | Flucrypyrim, a novel uterine relaxant, has antinociceptive and anti-inflammatory effects in vivo |
title_sort | flucrypyrim, a novel uterine relaxant, has antinociceptive and anti-inflammatory effects in vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318994/ https://www.ncbi.nlm.nih.gov/pubmed/28220794 http://dx.doi.org/10.1038/srep42040 |
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