The cyclooxygenase-2 product prostaglandin E2 modulates cardiac contractile function in adult rat ventricular cardiomyocytes

Klein, Aaron L.; Wold, Loren E.; Ren, Jun

doi:10.1016/j.phrs.2003.09.002

Cited by 9 publications

(6 citation statements)

References 15 publications

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“…Whether these differences relate to the different preparations used (isolated heart versus atrial and ventricular trabeculae) is not known. Moreover, Klein and Wold 4 used a system similar to the one used in our studies to observe that PGE 2 augmented peak shortening in adult rat cardiomyocytes independent of changes in calcium whereas concentrations greater than 10 −5 M reduced intracellular calcium. Church et al 10 also reported that PGE 2 (10 −5 M) increases the contraction frequency of neonatal rat cardiomyocytes but only spontaneous beating was measured.…”

Section: Discussionmentioning

confidence: 99%

“…Wang et al 3 showed that cardiomyocyte specific deletion of cyclooxygenase-2 increased ventricular tachycardia in response to electrical stimulation of the heart and infusion of PGE 2 was reported to depress premature ventricular beats in humans, consistent with its ability to reduce ischemia-induced arrhythmias in animal models. There is only one published paper describing the effect of PGE 2 on isolated rat myocytes in vitro and it found that PGE 2 increased contractility without effects on intracellular calcium 4 . However, these few reports do not allude to potential mechanisms by which PGE 2 increases the rate or force of contractions, including which PGE 2 receptor sub-type is involved.…”

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confidence: 99%

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Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor

Zhu

Bryson

et al. 2016

Circ: Heart Failure

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Background Prostaglandin E2 (PGE2) EP receptors EP3 and EP4 signal via decreased and increased cAMP production, respectively. Previously we reported that cardiomyocyte-specific EP4 KO mice develop dilated cardiomyopathy with reduced ejection fraction. We thus 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 (AVM). Isolated hearts of adult male C57Bl/6 mice were perfused with PGE2 (10−6M) or sulp (10−6M) and compared to vehicle. Both PGE2 and sulprostone decreased +dp/dt (p<0.01) and left ventricular developed pressure, LVDP, (p<0.001) with reversal by an EP3 antagonist. In contrast, the EP4 agonist had the opposite effect. AVM contractility was also reduced after treatment with either PGE2 or sulprostone for 10 min. We then examined the acute effects of PGE2, sulprostone and the EP4 agonist on expression of phosphorylated phospholamban (PLN) and SERCA2a in AVM using Western blot. Treatment with either PGE2 or sulprostone decreased expression of phosphorylated PLN corrected to total PLN whereas treatment with the EP4 agonist had the opposite effect. SERCA2a expression was unaffected. Finally, we examined the effect of these compounds in vivo using pressure volume loops. Both PGE2 and sulprostone decreased +dp/dt while the EP4 agonist increased +dp/dt. Conclusions Contractility is reduced via the EP3 receptor but increased via EP4. These effects may be mediated through changes in PLN phosphorylation and has relevance to detrimental effects of inflammation.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor

Zhu

Bryson

et al. 2016

Circ: Heart Failure

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“…Cardiac myocyte shortening measurements were done as described earlier [26,27] using the IonOptix system. The myocytes placed in tissue chambers (Cell microcontrols), were kept on the stage of the inverted microscope (Nikon TE-2000S).…”

Section: Methodsmentioning

confidence: 99%

Threonine-5 at the N-terminus can modulate sarcolipin function in cardiac myocytes

Bhupathy

Babu

Itô

et al. 2009

Journal of Molecular and Cellular Cardiology

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Sarcolipin (SLN) has emerged as an important regulator of the atrial sarcoplasmic reticulum (SR) Ca 2+ transport. The inhibitory effect of SLN on cardiac SR Ca 2+ ATPase (SERCA) pump can be relieved by β-adrenergic stimulation, which indicates that SLN is a reversible inhibitor. However, the mechanism of this reversible regulation of SERCA pump by SLN is yet to be determined. In the current study using adult rat ventricular myocytes we provide evidence that the threonine 5 (T5) residue at the N-terminus of SLN which is conserved among various species, critically regulates the SLN function. Point mutation of T5→alanine exerts an inhibitory effect on myocyte contractility and calcium transients similar to that of wild-type SLN, whereas mutation of T5→glutamic acid which mimics the phosphorylation abolished the inhibitory function of SLN. Our results showed that T5 can be phosphorylated in vitro by calcium-calmodulin dependent protein kinase II (CaMKII). Blocking the CaMKII activity in WT-SLN overexpressing myocytes using autocamtide inhibitory peptide completely abolished the β-adrenergic response. Taken together, our data suggest that T5 is the key amino acid which modulates SLN function via phosphorylation/dephosphorylation mechanisms through CaMKII pathway.

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“…Possible agonists of EP receptors are prostaglandin D 2 , E 2 or I 2 [5,31]. For all these prostaglandins, a negative inotropic effect on cardiac tissue is evidenced [32–34]. We therefore hypothesize that these prostaglandin subclasses, or analogous substances, possibly represent intermediate products in the effects of cardiodepressive mediators.…”

Section: Discussionmentioning

confidence: 99%