Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D₂ in the beating rat atrium.
10.4196/kjpp.2017.21.3.293
- Author:
Ying ZHANG
1
;
Xiang LI
;
Li Ping LIU
;
Lan HONG
;
Xia LIU
;
Bo ZHANG
;
Cheng Zhe WU
;
Xun CUI
Author Information
1. Department of Physiology, School of Medicine, Yanbian University, Yanji 133-002, China. cuixun@ybu.edu.cn 15526770645@163.com
- Publication Type:Original Article
- Keywords:
Atrial natriuretic peptide;
Mitogen-activated protein kinases;
Peroxisome proliferator-activated receptor γ;
Phosphatidylinositol-3-kinase;
Prostaglandin D₂
- MeSH:
Animals;
Atrial Natriuretic Factor*;
Heart;
Mitogen-Activated Protein Kinases;
Peroxisomes*;
Phosphotransferases;
PPAR gamma;
Protein Kinases;
Rats*
- From:The Korean Journal of Physiology and Pharmacology
2017;21(3):293-300
- CountryRepublic of Korea
- Language:English
-
Abstract:
Prostaglandin D₂ (PGD₂) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of PGD₂ 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 PGD₂ can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. PGD₂ (0.1 to 10 µM) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of PGD₂ on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 (1.0 µM) and AL-8810 (1.0 µM), PGD₂ and prostaglandin F2α (PGF2α) receptor antagonists, respectively. Moreover, PGD₂ clearly upregulated atrial peroxisome proliferator-activated receptor gamma (PPARγ) and the PGD₂ metabolite 15-deoxy-Δ12,14-PGJ₂ (15d-PGJ₂, 0.1 µM) dramatically increased atrial ANP secretion. Increased ANP secretions induced by PGD₂ and 15d-PGJ₂ 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 PGD₂. These results indicated that PGD₂ 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 PGD₂-induced atrial ANP secretion.
