Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D 2 in the beating rat atrium

• Published in: The Korean journal of physiology & pharmacology Vol. 21; no. 3; pp. 293 - 300
• Main Authors: Zhang, Ying, Li, Xiang, Liu, Li-Ping, Hong, Lan, Liu, Xia, Zhang, Bo, Wu, Cheng-Zhe, Cui, Xun
• Format: Journal Article
• Language: Korean
• Published: 대한생리학회-대한약리학회 01-01-2017; The Korean Journal of Physiology & Pharmacology Editorial Office
• Subjects: Phosphatidylinositol-3-kinase; Atrial natriuretic peptide; Peroxisome proliferator-activated receptorγ; Prostaglandin D 2; Mitogen-activated protein kinases; Prostaglandin $D_2; Peroxisome proliferator-activated receptor ${\gamma}
• ISSN: 1226-4512; 2093-3827

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 $10{\mu}M$) 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 ($1.0{\mu}M$) and AL-8810 ($1.0{\mu}M$), $PGD_2$ and prostaglandin $F2{\alpha}$ ($PGF2{\alpha}$) receptor antagonists, respectively. Moreover, $PGD_2$ clearly upregulated atrial peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and the $PGD_2$ metabolite 15-deoxy-${\Delta}12$, 14-$PGJ_2$ (15d-$PGJ_2$, $0.1{\mu}M$) dramatically increased atrial ANP secretion. Increased ANP secretions induced by $PGD_2$ and 15d-$PGJ_2$ were completely blocked by the $PPAR{\gamma}$ antagonist GW9662 ($0.1{\mu}M$). PD98059 ($10.0{\mu}M$) and LY294002 ($1.0{\mu}M$), 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 $PPAR{\gamma}$ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating $PGD_2$-induced atrial ANP secretion.