Korean J Physiol Pharmacol.  2017 May;21(3):293-300. 10.4196/kjpp.2017.21.3.293.

Peroxisome proliferator-activated receptor γ is essential for secretion of ANP induced by prostaglandin D₂ in the beating rat atrium

• Zhang Y
• Li X
• Liu LP
• Hong L
• Liu X
• Zhang B
• Wu CZ
• Cui X

• KMID: 2376957
• DOI: http://doi.org/10.4196/kjpp.2017.21.3.293

Abstract

Prostaglandin Dâ‚‚ (PGDâ‚‚) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of PGDâ‚‚ 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 PGDâ‚‚ can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. PGDâ‚‚ (0.1 to 10 µM) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of PGDâ‚‚ on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 (1.0 µM) and AL-8810 (1.0 µM), PGDâ‚‚ and prostaglandin F2α (PGF2α) receptor antagonists, respectively. Moreover, PGDâ‚‚ clearly upregulated atrial peroxisome proliferator-activated receptor gamma (PPARγ) and the PGDâ‚‚ metabolite 15-deoxy-Δ12,14-PGJâ‚‚ (15d-PGJâ‚‚, 0.1 µM) dramatically increased atrial ANP secretion. Increased ANP secretions induced by PGDâ‚‚ and 15d-PGJâ‚‚ 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 PGDâ‚‚. These results indicated that PGDâ‚‚ 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 PGDâ‚‚-induced atrial ANP secretion.

Keyword

Atrial natriuretic peptide; Mitogen-activated protein kinases; Peroxisome proliferator-activated receptor γ; Phosphatidylinositol-3-kinase; Prostaglandin D₂

MeSH Terms

Animals
Atrial Natriuretic Factor*
Heart
Mitogen-Activated Protein Kinases
Peroxisomes*
Phosphotransferases
PPAR gamma
Protein Kinases
Rats*
Atrial Natriuretic Factor
Mitogen-Activated Protein Kinases
PPAR gamma
Phosphotransferases
Protein Kinases

Figure

• 

  Fig. 1 Prostaglandin D2 (PGD2, 1.0 µM) significantly increased ANP secretion (A) and mechanical dynamics (B) in isolated perfused beating rat atria.Data were expressed as mean±SEM, n=6. *p<0.05 vs. control period.

• 

  Fig. 2 PGD2 promotes secretion of ANP (A) and mechanical dynamics (B) by dose-dependent manner in isolated beating rat atria.Data were expressed as mean±SEM, n=6 for each group. *p<0.05 vs. control (vehicle) group.

• 

  Fig. 3 Effects of PGD2 and PGF2α receptor antagonists on PGD2-increased atrial ANP secretion and mechanical dynamics in isolated beating rat atria.AH6809 (AH, 1.0 µM), an antagonist of PGD2 receptor; AL8810 (AL, 1.0 µM), an antagonist of PGF2α receptor. Data were expressed as mean±SEM, n=6 for each group.

• 

  Fig. 4 Effect of AH6809 (AH, 1.0 µM) on 15d-PGJ2 (0.1 µM)-induced atrial ANP and dynamics in isolated beating rat atria.Data were expressed as mean±SEM, n=6 for each group. *p<0.05 vs. control period.

• 

  Fig. 5 GW 9662 (GW, 0.1 µM), an antagonist of PPARγ, inhibited the atrial secretion of ANP (Aa, Ba) and dynamics (Ab, Bb) induced by 15d-PGJ2 and PGD2 in isolated beating rat atria.Data were expressed as mean±SEM, n=6 for each group.

• 

  Fig. 6 Effect of PGD2 on PPARγ expression in isolated beating rat atria.Data are means±SEM, n=5 for each group. GW, GW9662 (0.1 µM). *p<0.05 vs. control group; #p<0.05 vs. PGD2 group.

• 

  Fig. 7 Effects of PD98059 (PD, 10.0 µM, A) and LY294002 (LY, 1.0 µM, B) on PGD2-induced atrial secretion of ANP and dynamics in isolated beating rat atria.Data were expressed as mean±SEM, n=6 for each group. *p<0.05 vs. control period.

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