Evidence map›Paper›PMID 26493129›Full record

ArticleBritish journal of pharmacology2016

Mirabegron relaxes urethral smooth muscle by a dual mechanism involving β3 -adrenoceptor activation and α1 -adrenoceptor blockade.

E C Alexandre, L R Kiguti, F B Calmasini, F H Silva, K P da Silva, R Ferreira, C A Ribeiro, F Z Mónica, A S Pupo, E Antunes

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 2 pooled it
7.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. βNeurourology and urodynamics · 2025
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Adrenoceptors in the Lower Urinary Tract.Handbook of experimental pharmacology · 2024
    Review
  12. Article
  13. Article
  14. Review
  15. Is the βBiomolecules · 2023
    Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

E C AlexandreDepartment of Pharmacology, University of Campinas (UNICAMP), Campinas, Brazil.
L R KigutiDepartment of Pharmacology, Institute of Biosciences, University of São Paulo State (UNESP), Botucatu, São Paulo, Brazil.
F B CalmasiniDepartment of Pharmacology, University of Campinas (UNICAMP), Campinas, Brazil.
F H SilvaDepartment of Pharmacology, University of Campinas (UNICAMP), Campinas, Brazil.
K P da SilvaDepartment of Pharmacology, Institute of Biosciences, University of São Paulo State (UNESP), Botucatu, São Paulo, Brazil.
R FerreiraHematology and Hemotherapy Center, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.
C A RibeiroDepartment of Pharmacology, Institute of Biosciences, University of São Paulo State (UNESP), Botucatu, São Paulo, Brazil.
F Z MónicaDepartment of Pharmacology, University of Campinas (UNICAMP), Campinas, Brazil.
A S PupoDepartment of Pharmacology, Institute of Biosciences, University of São Paulo State (UNESP), Botucatu, São Paulo, Brazil.
E AntunesDepartment of Pharmacology, University of Campinas (UNICAMP), Campinas, Brazil.
Universidade Estadual de Campinas (UNICAMP) · BRUniversidade de São Paulo · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

linked articleThis article is commented on by Michel, M. C., pp. 429-430 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.13379. BACKGROUND AND PURPOSE: Mirabegron is the first β3 -adrenoceptor agonist approved for treatment of overactive bladder syndrome. This study aimed to investigate the effects of β3 -adrenoceptor agonist mirabegron in mouse urethra. The possibility that mirabegron also exerts α1 -adrenoceptor antagonism was also tested in rat smooth muscle preparations presenting α1A - (vas deferens and prostate), α1D - (aorta) and α1B -adrenoceptors (spleen). EXPERIMENTAL APPROACH: Functional assays were carried out in mouse and rat isolated tissues. Competition assays for the specific binding of [(3) H]prazosin to membrane preparations of HEK-293 cells expressing each of the human α1 -adrenoceptors, as well as β-adrenoceptor mRNA expression and cyclic AMP measurements in mouse urethra, were performed. KEY

resultsMirabegron produced concentration-dependent urethral relaxations that were shifted to the right by the selective β3 -adrenoceptor antagonist L-748,337 but unaffected by β1 - and β2 -adrenoceptor antagonists (atenolol and ICI-118,551 respectively). Mirabegron-induced relaxations were enhanced by the PDE4 inhibitor rolipram, and the agonist stimulated cAMP synthesis. Mirabegron also produced rightward shifts in urethral contractions induced by the α1 -adrenoceptor agonist phenylephrine. Schild regression analysis revealed that mirabegron behaves as a competitive antagonist of α1 -adrenoceptors in urethra, vas deferens and prostate (α1A -adrenoceptor, pA2  ≅ 5.6) and aorta (α1D -adrenoceptor, pA2  ≅ 5.4) but not in spleen (α1B -adrenoceptor). The affinities estimated for mirabegron in functional assays were consistent with those estimated in radioligand binding with human recombinant α1A - and α1D -adrenoceptors (pKi  ≅ 6.0). CONCLUSION AND IMPLICATIONS: The effects of mirabegron in urethral smooth muscle are the result of β3 -adrenoceptor agonism together with α1A and α1D -adrenoceptor antagonism.

Indexed as

AcetanilidesAdrenergic alpha-1 Receptor AntagonistsAdrenergic beta-3 Receptor AgonistsAminophenolsAnimalsAorta, ThoracicHEK293 CellsHumansIn Vitro TechniquesMaleMice, Inbred C57BLMuscle RelaxationMuscle, SmoothProstateRats, WistarReceptors, Adrenergic, alphaAcetanilidesAdrenergic alpha-1 Receptor AntagonistsAdrenergic beta-3 Receptor AgonistsAminophenolsL 748,337mirabegronReceptors, Adrenergic, alphaSulfonamidesThiazoles

Identifiers

PMID26493129
PMCPMC4728418
OpenAlexW1945095845

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.