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Updated: Sep 26, 2025
Bladder Smooth Muscle Strip Contractility as a Method to Evaluate Lower Urinary Tract Pharmacology
Published on: August 18, 2014
Mirabegron attenuates porcine ureteral contractility via α1-adrenoceptor antagonism
Iris Lim1, Russ Chess-Williams2
1Centre for Urology Research, Faculty of Health Science & Medicine, Bond University, Robina, QLD, 4229, Australia. ilim@bond.edu.au.
Abstract:
The β3-agonist mirabegron is thought to induce relaxation of the detrusor muscle, contributing to the improvement of overactive bladder symptoms. There has been recent interest in purposing mirabegron as a medical expulsive therapy drug to improve the passage of smaller kidney stones by relaxing the ureteral smooth muscles. The aim of this study was to determine the effects of mirabegron on the activity of the ureter. Additionally, we investigated the receptor and mechanisms through which mirabegron exerts these effects. In vitro agonist-induced responses of isolated porcine distal ureteral tissues were measured in the absence and presence of mirabegron in organ bath experiments. The responses were expressed as frequency, area under the curve and maximum amplitude. Mirabegron at concentrations of 100 nM and lower failed to suppress phenylephrine- or 5-HT-induced contractions in the porcine ureteral strip. Mirabegron at 1 μM and 10 μM produced a rightward shift of phenylephrine concentration-response curves in these tissues. This effect of mirabegron (10 μM) was not present in 5-HT concentration-response curves. The mirabegron effect on phenylephrine-induced contractions was also not abolished by β-adrenoceptor antagonist SR 59230A (10 μM), β-adrenoceptor antagonist propranolol (10 μM), α2-adrenoceptor antagonist yohimbine (30 nM), and nitric oxide synthase inhibitor L-NNA (10 μM). The present results show that mirabegron suppresses ureteral contractile responses in the porcine ureter via α1-adrenoceptor antagonism, since their effects were not present when the tissues were contracted with 5-HT. Furthermore, the inhibitory effects by mirabegron were not affected by β3-adrenoceptor antagonists.
Insights
Mirabegron, used for overactive bladder, may help kidney stones by relaxing ureteral muscles. This study found mirabegron suppresses ureteral contractions via alpha-1 adrenoceptor antagonism, not beta-3 agonism.
Area of Science:
- Pharmacology
- Urology
- Nephrology
Background:
- Mirabegron, a beta-3 agonist, relaxes the detrusor muscle for overactive bladder.
- Mirabegron is being explored for medical expulsive therapy for kidney stones due to potential ureteral smooth muscle relaxation.
- The precise mechanism of mirabegron's effect on ureteral activity is not fully understood.
Purpose of the Study:
- To investigate the effects of mirabegron on porcine ureteral tissue activity.
- To identify the specific receptors and mechanisms through which mirabegron influences ureteral function.
Main Methods:
- In vitro organ bath experiments using isolated porcine distal ureteral tissues.
- Measurement of agonist-induced contractions (frequency, area under the curve, maximum amplitude) in the presence and absence of mirabegron.
- Assessment of mirabegron's effects in conjunction with various receptor antagonists and inhibitors.
Main Results:
- Mirabegron (1 µM and 10 µM) inhibited phenylephrine-induced contractions, causing a rightward shift in concentration-response curves.
- Mirabegron's inhibitory effect on phenylephrine contractions was not blocked by beta-adrenoceptor antagonists, alpha-2 adrenoceptor antagonists, or nitric oxide synthase inhibitors.
- The observed effects were specific to alpha-1 adrenoceptor-mediated contractions, as mirabegron did not affect 5-HT-induced contractions and its effects were not mediated by beta-3 adrenoceptors.
Conclusions:
- Mirabegron suppresses ureteral contractile responses in porcine ureters.
- The mechanism involves antagonism of alpha-1 adrenoceptors, not beta-3 adrenoceptor agonism.
- These findings suggest a potential role for mirabegron in managing conditions involving ureteral smooth muscle activity, such as kidney stone passage.
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