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β 3 ‐Adrenoceptors in the normal and diseased urinary bladder—What are the open questions?
Author(s) -
Igawa Yasuhiko,
Aizawa Naoki,
Michel Martin C.
Publication year - 2019
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14658
Subject(s) - mirabegron , detrusor muscle , agonist , overactive bladder , urinary bladder , stimulation , endocrinology , medicine , mechanism of action , clonidine , adrenergic receptor , adrenergic , urinary system , muscle relaxation , chemistry , receptor , pathology , in vitro , biochemistry , alternative medicine
β 3 -Adrenoceptor agonists are used in the treatment of overactive bladder syndrome. Although the relaxant response to adrenergic stimulation in human detrusor smooth muscle cells is mediated mainly via β 3 -adrenoceptors, the plasma concentrations of the therapeutic dose of mirabegron, the only clinically approved β 3 -adrenoceptor agonist, are considerably lower than the EC 50 for causing direct relaxation of human detrusor, suggesting a mechanism of action other than direct relaxation of detrusor smooth muscle. However, the site and mechanism of action of β 3 -adrenoceptor agonists in the bladder have not been firmly established. Postulated mechanisms include prejunctional suppression of ACh release from the parasympathetic nerves during the storage phase and inhibition of micro-contractions through β 3 -adrenoceptors on detrusor smooth muscle cells or suburothelial interstitial cells. Implications of possible desensitization of β 3 -adrenoceptors in the bladder upon prolonged agonist exposure and possible causes of rarely observed cardiovascular effects of mirabegron are also discussed. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.