The beta-3 adrenoceptor agonist, mirabegron relaxes isolated prostate from human and rabbit: new therapeutic indication?
Prostate
; 75(4): 440-7, 2015 Mar 01.
Article
in En
| MEDLINE
| ID: mdl-25417911
ABSTRACT
BACKGROUND:
Alpha1 (α1)-blockers, 5-alpha reductase and phosphodiesterase type-5 inhibitors are pharmacological classes currently available for benign prostatic hyperplasia (BPH) treatment. Mirabegron, a beta-3 adrenoceptor (ß3-AR) agonist has been approved for the therapy of overactive bladder and may constitute a new therapeutic option for BPH treatment. This study is aimed to evaluate the in vitro effects of mirabegron in human and rabbit prostatic smooth muscle.METHODS:
In rabbit prostate, electrical field stimulation (EFS)-induced contraction and concentration-response curve (CRC) to mirabegron in phenylephrine pre-contracted tissues were carried out. The potency (pEC50 ) and maximal response (Emax ) values were determined. In human prostate, CRC to phenylephrine was carried out in the absence and presence of mirabegron. Immunohistochemistry analysis for ß3-AR was also carried out.RESULTS:
In human prostate, immunohistochemistry analysis revealed the presence of ß3-AR on the transition zone and mirabegron reduced by 42% the phenylephrine-induced contractions. In rabbit prostate, mirabegron produced concentration-dependent relaxations (pEC50 6.01 ± 0.12; Emax 106 ± 3%), which were fully resistant to the blockade of ß1-AR and ß2-AR. The ß3-AR blocker L748,337 caused a six-fold rightward shift in mirabegron-induced relaxations. Mirabegron (10 µM) reduced by 63% the EFS-induced contractions. Inhibitors of nitric oxide (L-NAME) and of soluble guanylate cyclase (ODQ) along with a cocktail of K+ channel blockers (apamin, charybdotoxin, glibenclamide, tetraethylammonium) all failed to significantly affect the mirabegron-induced rabbit relaxations.CONCLUSION:
Mirabegron relaxes prostatic smooth muscle, providing an experimental support for the clinical investigation of its combination with an α1-blockers or PDE5 inhibitors in the treatment of BPH. Prostate 75440-447, 2015. © 2014 Wiley Periodicals, Inc.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostate
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Thiazoles
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Adrenergic beta-3 Receptor Agonists
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Acetanilides
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Muscle Relaxation
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Muscle, Smooth
Limits:
Animals
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Humans
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Male
Language:
En
Journal:
Prostate
Year:
2015
Document type:
Article
Affiliation country:
Brazil