ArticleThe Journal of clinical investigation2008
beta3-adrenergic receptor activation increases human atrial tissue contractility and stimulates the L-type Ca2+ current.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 104 citations in OpenAlex.
- Cardiovascular safety of vibegron, a new β3-adrenoceptor agonist, in older patients with overactive bladder: Post-hoc analysis of a randomized, placebo-controlled, double-blind comparative phase 3 study.Neurourology and urodynamics · 2021Trial
- Cardiovascular safety of mirabegron add-on therapy to tamsulosin for the treatment of overactive bladder in men with lower urinary tract symptoms: A post hoc analysis from the MATCH study.Lower urinary tract symptoms · 2021Trial
- Cardiovascular safety of antimuscarinic add-on therapy in patients with overactive bladder who had a suboptimal response to mirabegron monotherapy: A post hoc analysis from the Japanese MILAI II study.Lower urinary tract symptoms · 2020Trial
- Cardiovascular safety in refractory incontinent patients with overactive bladder receiving add-on mirabegron therapy to solifenacin (BESIDE).International journal of clinical practice · 2017Trial
- Efficacy and Safety of Mirabegron in Frail Older Adults with Overactive Bladder.Drugs & aging · 2026Review
- Therapeutic Potential of the β3-Adrenergic Receptor and Its Ligands in Cardiovascular Diseases.International journal of molecular sciences · 2025Review
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- Physiological and metabolic functions of the βJournal of physiology and biochemistry · 2024Review
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- Inside the Biology of the β3-Adrenoceptor.Biomolecules · 2024Review
- The βAdvances in pharmacological and pharmaceutical sciences · 2024Review
- Therapeutic Potential for Beta-3 Adrenoreceptor Agonists in Peripheral Arterial Disease and Diabetic Foot Ulcers.Biomedicines · 2023Review
- Status of βReviews in cardiovascular medicine · 2023Review
- Autonomic Nervous System Regulation of Epicardial Adipose Tissue: Potential Roles for Regulator of G Protein Signaling-4.Current issues in molecular biology · 2022Review
- Mirabegron, a β3‑adrenoreceptor agonist, regulates right and left atrial arrhythmogenesis differently.Experimental and therapeutic medicine · 2022Article
- The goldfish Carassius auratus: an emerging animal model for comparative cardiac research.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2022Review
- Review
- Understanding How Phosphorylation and Redox Modifications Regulate Cardiac Ryanodine Receptor Type 2 Activity to Produce an Arrhythmogenic Phenotype in Advanced Heart Failure.ACS pharmacology & translational science · 2020Review
- Cardiac βBritish journal of pharmacology · 2019Review
- Everything You Always Wanted to Know about βCells · 2019Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
beta3-adrenergic receptor (beta3-AR) activation produces a negative inotropic effect in human ventricles. Here we explored the role of beta3-AR in the human atrium. Unexpectedly, beta3-AR activation increased human atrial tissue contractility and stimulated the L-type Ca2+ channel current (I Ca,L) in isolated human atrial myocytes (HAMs). Right atrial tissue specimens were obtained from 57 patients undergoing heart surgery for congenital defects, coronary artery diseases, valve replacement, or heart transplantation. The I(Ca,L) and isometric contraction were recorded using a whole-cell patch-clamp technique and a mechanoelectrical force transducer. Two selective beta3-AR agonists, SR58611 and BRL37344, and a beta3-AR partial agonist, CGP12177, stimulated I(Ca,L) in HAMs with nanomolar potency and a 60%-90% efficacy compared with isoprenaline. The beta3-AR agonists also increased contractility but with a much lower efficacy (approximately 10%) than isoprenaline. The beta3-AR antagonist L-748,337, beta1-/beta2-AR antagonist nadolol, and beta1-/beta2-/beta3-AR antagonist bupranolol were used to confirm the involvement of beta3-ARs (and not beta1-/beta2-ARs) in these effects. The beta3-AR effects involved the cAMP/PKA pathway, since the PKA inhibitor H89 blocked I(Ca,L) stimulation and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) strongly increased the positive inotropic effect. Therefore, unlike in ventricular tissue, beta3-ARs are positively coupled to L-type Ca2+ channels and contractility in human atrial tissues through a cAMP-dependent pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.