Related Experiment Video
Updated: Mar 1, 2026
Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
The β3 -adrenoceptor agonist mirabegron increases human atrial force through β1 -adrenoceptors: an indirect
Weilan Mo1,2,3, Martin C Michel4, Xiang Wen Lee2
1School of Biomedical Sciences, Queensland University of Technology, Brisbane, Qld, Australia.
Background And Purpose:
Mirabegron has been classified as a β3 -adrenoceptor agonist approved for overactive bladder syndrome. We investigated possible cardiac effects of mirabegron in the absence or presence of β-adrenoceptor subtype antagonists. In view of its phenylethanolamine structure, we investigated whether mirabegron has indirect sympathomimetic activity by using neuronal uptake blockers.
Experimental Approach:
Right atrial trabeculae, from non-failing hearts, were paced and contractile force measured at 37°C. Single concentrations of mirabegron were added in the absence or presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), β3 (L-748,337), β1 (CGP 20712A), β2 (ICI 118,551) -adrenoceptor antagonists, neuronal uptake inhibitors desipramine or phenoxybenzamine.
Key Results:
Mirabegron significantly increased contractile force in human right atrium (1 μM, 7.6 ± 2.6%, n = 7; 10 μM, 10.2 ± 1.5%, n = 22 compared with (-)-isoprenaline P < 0.05). In the presence of IBMX, mirabegron (10 μM) caused a greater contraction. L-748,337 (100 nM) had no effect on the increase in contractile force caused by mirabegron (10 μM). In contrast, mirabegron (10 μM) reduced contractile force in the presence of CGP 20712A, which was not affected by L-748,337 (100 nM) or ICI 118,551 (50 nM). Mirabegron (10 μM) also reduced contractile force in the presence of desipramine or phenoxybenzamine.
Conclusions And Implications:
Mirabegron increases human atrial force through β1 - but not β3 -adrenoceptors. Desipramine and phenoxybenzamine block neuronal uptake and conceivably prevent mirabegron from releasing noradrenaline. A non-specific cardiodepressant effect is not mediated through β3 (or β2 )-adrenoceptors, consistent with lack of β3 -adrenoceptor function on human atrial contractility.
Insights
Mirabegron increases human atrial contractility via beta-1 (β1) adrenoceptors, not beta-3 (β3) receptors. It may also have indirect sympathomimetic activity, but this is blocked by neuronal uptake inhibitors.
Area of Science:
- Pharmacology
- Cardiology
Background:
- Mirabegron is a beta-3 (β3) adrenoceptor agonist used for overactive bladder.
- Its phenylethanolamine structure suggests potential indirect sympathomimetic activity.
Purpose of the Study:
- To investigate the cardiac effects of mirabegron.
- To determine if mirabegron acts via β-adrenoceptor subtypes or has indirect sympathomimetic activity.
Main Methods:
- Human right atrial trabeculae were paced to measure contractile force.
- Mirabegron was tested alone and with β-adrenoceptor antagonists (β3, β1, β2) and neuronal uptake inhibitors.
Main Results:
- Mirabegron increased contractile force via β1-adrenoceptors.
- It did not increase force via β3-adrenoceptors.
- Neuronal uptake inhibitors blocked mirabegron's effects, suggesting prevention of noradrenaline release.
Conclusions:
- Mirabegron's positive inotropic effect on human atria is mediated by β1-adrenoceptors.
- Mirabegron does not appear to function through β3-adrenoceptors on human atrial contractility.
- Indirect sympathomimetic activity is likely blocked by neuronal uptake inhibition.
More Related Videos
Related Concept Videos
01:30Adrenergic Agonists: Direct-Acting Agents
These agents can be classified...
01:26Adrenergic Receptors: β Subtype
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
00:59Direct-Acting Cholinergic Agonists: Pharmacological Actions
01:25Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral...
01:17Antihypertensive Drugs: Action of β1 Blockers
01:22Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally,...