Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor
Gu X, Xu J, Zhu L, Bryson T, Yang XP, Peterson E, Harding P. Prostaglandin e2 reduces cardiac contractility via ep3 receptor. Circ Heart Fail. 2016 ;9(8). pii: e003291.
Circ Heart Fail
BACKGROUND: Prostaglandin E2 (PGE2) EP receptors EP3 and EP4 signal via decreased and increased cAMP production, respectively. Previously, we reported that cardiomyocyte-specific EP4 knockout mice develop dilated cardiomyopathy with reduced ejection fraction. Thus, we hypothesized that PGE2 increases contractility via EP4 but decreases contractility via EP3.
METHODS AND RESULTS: The effects of PGE2 and the EP1/EP3 agonist sulprostone on contractility were examined in the mouse Langendorff preparation and in adult mouse cardiomyocytes. Isolated hearts of adult male C57Bl/6 mice were perfused with PGE2 (10(-6) M) or sulprostone (10(-6) M) and compared with vehicle. Both PGE2 and sulprostone decreased +dp/dt (P
CONCLUSIONS: Contractility is reduced via the EP3 receptor but increased via EP4. These effects may be mediated through changes in phospholamban phosphorylation and has relevance to detrimental effects of inflammation.
Medical Subject Headings
Animals; Calcium-Binding Proteins; Cells, Cultured; Dinoprostone; Isolated Heart Preparation; Male; Mice, Inbred C57BL; Myocardial Contraction; Myocytes, Cardiac; Phosphorylation; Receptors, Prostaglandin E, EP3 Subtype; Receptors, Prostaglandin E, EP4 Subtype; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Signal Transduction; Ventricular Function, Left; Ventricular Pressure