ArticleAmerican journal of physiology. Heart and circulatory physiology2014
Urocortin 2 stimulates nitric oxide production in ventricular myocytes via Akt- and PKA-mediated phosphorylation of eNOS at serine 1177.
Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Effect of 3-caffeoyl, 4-dihydrocaffeoylquinic acid fromToxicological research · 2022Article
- Urocortin Role in Ischemia Cardioprotection and the Adverse Cardiac Remodeling.International journal of molecular sciences · 2021Review
- Vasodilatory Effect of Guanxinning Tablet on Rabbit Thoracic Aorta is Modulated by Both Endothelium-Dependent and -Independent Mechanism.Frontiers in pharmacology · 2021Article
- Acid sphingomyelinase downregulation alleviates vascular endothelial leptin resistance in rats.Acta pharmacologica Sinica · 2020Article
- Altered calcium handling produces reentry-promoting action potential alternans in atrial fibrillation-remodeled hearts.JCI insight · 2020Article
- Effect of omentin on cardiovascular functions and gene expressions in isolated rat hearts.Anatolian journal of cardiology · 2019Article
- Structural and functional cardiac profile after prolonged duration of mechanical unloading: potential implications for myocardial recovery.American journal of physiology. Heart and circulatory physiology · 2018Article
- Article
- Targeting β3-Adrenergic Receptors in the Heart: Selective Agonism and β-Blockade.Journal of cardiovascular pharmacology · 2017Review
- Targeting endothelial connexin40 inhibits tumor growth by reducing angiogenesis and improving vessel perfusion.Oncotarget · 2016Article
- Urocortin Treatment Improves Acute Hemodynamic Instability and Reduces Myocardial Damage in Post-Cardiac Arrest Myocardial Dysfunction.PloS one · 2016Article
- Research on the Effects of the Chronic Treatment With Different Doses of Urocortin 2 in Heart Failure Rats.Dose-response : a publication of International Hormesis SocietyArticle
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Authors and funding
15 authors at 8 institutions in 4 countries.
Funding
Abstract
Urocortin 2 (Ucn2) is a cardioactive peptide exhibiting beneficial effects in normal and failing heart. In cardiomyocytes, it elicits cAMP- and Ca(2+)-dependent positive inotropic and lusitropic effects. We tested the hypothesis that, in addition, Ucn2 activates cardiac nitric oxide (NO) signaling and elucidated the underlying signaling pathways and mechanisms. In isolated rabbit ventricular myocytes, Ucn2 caused concentration- and time-dependent increases in phosphorylation of Akt (Ser473, Thr308), endothelial NO synthase (eNOS) (Ser1177), and ERK1/2 (Thr202/Tyr204). ERK1/2 phosphorylation, but not Akt and eNOS phosphorylation, was suppressed by inhibition of MEK1/2. Increased Akt phosphorylation resulted in increased Akt kinase activity and was mediated by corticotropin-releasing factor 2 (CRF2) receptors (astressin-2B sensitive). Inhibition of phosphatidylinositol 3-kinase (PI3K) diminished both Akt as well as eNOS phosphorylation mediated by Ucn2. Inhibition of protein kinase A (PKA) reduced Ucn2-induced phosphorylation of eNOS but did not affect the increase in phosphorylation of Akt. Conversely, direct receptor-independent elevation of cAMP via forskolin increased phosphorylation of eNOS but not of Akt. Ucn2 increased intracellular NO concentration ([NO]i), [cGMP], [cAMP], and cell shortening. Inhibition of eNOS suppressed the increases in [NO]i and cell shortening. When both PI3K-Akt and cAMP-PKA signaling were inhibited, the Ucn2-induced increases in [NO]i and cell shortening were attenuated. Thus, in rabbit ventricular myocytes, Ucn2 causes activation of cAMP-PKA, PI3K-Akt, and MEK1/2-ERK1/2 signaling. The MEK1/2-ERK1/2 pathway is not required for stimulation of NO signaling in these cells. The other two pathways, cAMP-PKA and PI3K-Akt, converge on eNOS phosphorylation at Ser1177 and result in pronounced and sustained cellular NO production with subsequent stimulation of cGMP signaling.
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