ArticleEuropean journal of pharmacology2012
MRP4 and CFTR in the regulation of cAMP and β-adrenergic contraction in cardiac myocytes.
Article in European journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Structural basis of human ABCC4 recognition of cAMP and ligand recognition flexibility.Cell & bioscience · 2025Article
- Pharmacological Modulation of the CaPharmaceuticals (Basel, Switzerland) · 2023Article
- Pharmacological Modulation by Low Molecular Weight Heparin of Purinergic Signaling in Cardiac Cells Prevents Arrhythmia and Lethality Induced by Myocardial Infarction.Journal of cardiovascular development and disease · 2023Article
- Role of cardiac βClinics (Sao Paulo, Brazil) · 2023Article
- TIMP3 induces gene expression partly through PI3K and their association with vascularization and heart rate.Frontiers in cardiovascular medicine · 2023Article
- Pharmacodynamic properties for inhibition of cAMP- and cGMP elimination by pentoxifylline remain unaltered in vitro during hypothermia.Scandinavian journal of trauma, resuscitation and emergency medicine · 2022Article
- Treatment of Cardiovascular Dysfunction With PDE5-Inhibitors - Temperature Dependent Effects on Transport and Metabolism of cAMP and cGMP.Frontiers in physiology · 2021Article
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- ABC Transport Proteins in Cardiovascular Disease-A Brief Summary.Molecules (Basel, Switzerland) · 2017Review
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- Impaired cardiac and peripheral hemodynamic responses to inhaled β₂-agonist in cystic fibrosis.Respiratory research · 2015Article
- Cardiac cAMP: production, hydrolysis, modulation and detection.Frontiers in pharmacology · 2015Review
- New perspectives in signaling mediated by receptors coupled to stimulatory G protein: the emerging significance of cAMP efflux and extracellular cAMP-adenosine pathway.Frontiers in pharmacology · 2015Review
- Förster resonance energy transfer - an approach to visualize the spatiotemporal regulation of macromolecular complex formation and compartmentalized cell signaling.Biochimica et biophysica acta · 2014Review
- Compartmentalization of β-adrenergic signals in cardiomyocytes.Trends in cardiovascular medicine · 2013Review
- Left ventricular and aortic dysfunction in cystic fibrosis mice.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2013Article
- Multi-drug resistance protein 4 (MRP4)-mediated regulation of fibroblast cell migration reflects a dichotomous role of intracellular cyclic nucleotides.The Journal of biological chemistry · 2013Article
- Cyclic nucleotide compartmentalization: contributions of phosphodiesterases and ATP-binding cassette transporters.Annual review of pharmacology and toxicology · 2013Review
- The relationship between cardiac hemodynamics and exercise tolerance in cystic fibrosis.Heart & lung : the journal of critical careArticle
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Spatiotemporal regulation of cAMP in cardiac myocytes is integral to regulating the diverse functions downstream of β-adrenergic stimulation. The activities of cAMP phosphodiesterases modulate critical and well-studied cellular processes. Recently, in epithelial and smooth muscle cells, it was found that the multi-drug resistant protein 4 (MRP4) acts as a cAMP efflux pump to regulate intracellular cAMP levels and alter effector function, including activation of the cAMP-stimulated Cl(-) channel, CFTR (cystic fibrosis transmembrane conductance regulator). In the current study we investigated the potential role of MRP4 in regulating intracellular cAMP and β-adrenergic stimulated contraction rate in cardiac myocytes. Cultured neonatal ventricular myocytes were used for all experiments. In addition to wildtype mice, β(1)-, β(2)-, and β(1)/β(2)-adrenoceptor, and CFTR knockout mice were used. MRP4 expression was probed via Western blot, intracellular cAMP was measured by fluorescence resonance energy transfer, while the functional role of MRP4 was assayed via monitoring of isoproterenol-stimulated contraction rate. We found that MRP4 is expressed in mouse neonatal ventricular myocytes. A pharmacological inhibitor of MRP4, MK571, potentiated submaximal isoproterenol-stimulated cAMP accumulation and cardiomyocyte contraction rate via β(1)-adrenoceptors. CFTR expression was critical for submaximal isoproterenol-stimulated contraction rate. Interestingly, MRP4-dependent changes in contraction rate were CFTR-dependent, however, PDE4-dependent potentiation of contraction rate was CFTR-independent. We have shown, for the first time, a role for MRP4 in the regulation of cAMP in cardiac myocytes and involvement of CFTR in β-adrenergic stimulated contraction. Together with phosphodiesterases, MRP4 must be considered when examining cAMP regulation in cardiac myocytes.
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