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Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D(2) in the beating rat atrium
Prostaglandin D(2) (PGD(2)) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of PGD(2) in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the presen...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Physiological Society and The Korean Society of Pharmacology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409115/ https://www.ncbi.nlm.nih.gov/pubmed/28461771 http://dx.doi.org/10.4196/kjpp.2017.21.3.293 |
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author | Zhang, Ying Li, Xiang Liu, Li-Ping Hong, Lan Liu, Xia Zhang, Bo Wu, Cheng-Zhe Cui, Xun |
author_facet | Zhang, Ying Li, Xiang Liu, Li-Ping Hong, Lan Liu, Xia Zhang, Bo Wu, Cheng-Zhe Cui, Xun |
author_sort | Zhang, Ying |
collection | PubMed |
description | Prostaglandin D(2) (PGD(2)) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of PGD(2) in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether PGD(2) can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. PGD(2) (0.1 to 10 µM) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of PGD(2) on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 (1.0 µM) and AL-8810 (1.0 µM), PGD(2) and prostaglandin F2α (PGF2α) receptor antagonists, respectively. Moreover, PGD(2) clearly upregulated atrial peroxisome proliferator-activated receptor gamma (PPARγ) and the PGD(2) metabolite 15-deoxy-Δ12,14-PGJ(2) (15d-PGJ(2), 0.1 µM) dramatically increased atrial ANP secretion. Increased ANP secretions induced by PGD(2) and 15d-PGJ(2) were completely blocked by the PPARγ antagonist GW9662 (0.1 µM). PD98059 (10.0 µM) and LY294002 (1.0 µM), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by PGD(2). These results indicated that PGD(2) stimulated atrial ANP secretion and promoted positive inotropy by activating PPARγ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating PGD(2)-induced atrial ANP secretion. |
format | Online Article Text |
id | pubmed-5409115 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Korean Physiological Society and The Korean Society of Pharmacology |
record_format | MEDLINE/PubMed |
spelling | pubmed-54091152017-05-02 Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D(2) in the beating rat atrium Zhang, Ying Li, Xiang Liu, Li-Ping Hong, Lan Liu, Xia Zhang, Bo Wu, Cheng-Zhe Cui, Xun Korean J Physiol Pharmacol Original Article Prostaglandin D(2) (PGD(2)) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of PGD(2) in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether PGD(2) can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. PGD(2) (0.1 to 10 µM) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of PGD(2) on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 (1.0 µM) and AL-8810 (1.0 µM), PGD(2) and prostaglandin F2α (PGF2α) receptor antagonists, respectively. Moreover, PGD(2) clearly upregulated atrial peroxisome proliferator-activated receptor gamma (PPARγ) and the PGD(2) metabolite 15-deoxy-Δ12,14-PGJ(2) (15d-PGJ(2), 0.1 µM) dramatically increased atrial ANP secretion. Increased ANP secretions induced by PGD(2) and 15d-PGJ(2) were completely blocked by the PPARγ antagonist GW9662 (0.1 µM). PD98059 (10.0 µM) and LY294002 (1.0 µM), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by PGD(2). These results indicated that PGD(2) stimulated atrial ANP secretion and promoted positive inotropy by activating PPARγ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating PGD(2)-induced atrial ANP secretion. The Korean Physiological Society and The Korean Society of Pharmacology 2017-05 2017-04-21 /pmc/articles/PMC5409115/ /pubmed/28461771 http://dx.doi.org/10.4196/kjpp.2017.21.3.293 Text en Copyright © Korean J Physiol Pharmacol http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Zhang, Ying Li, Xiang Liu, Li-Ping Hong, Lan Liu, Xia Zhang, Bo Wu, Cheng-Zhe Cui, Xun Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D(2) in the beating rat atrium |
title | Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D(2) in the beating rat atrium |
title_full | Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D(2) in the beating rat atrium |
title_fullStr | Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D(2) in the beating rat atrium |
title_full_unstemmed | Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D(2) in the beating rat atrium |
title_short | Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D(2) in the beating rat atrium |
title_sort | peroxisome proliferator-activated receptor γ is essential for secretion of anp induced by prostaglandin d(2) in the beating rat atrium |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409115/ https://www.ncbi.nlm.nih.gov/pubmed/28461771 http://dx.doi.org/10.4196/kjpp.2017.21.3.293 |
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