Beta adrenergic modulation of spontaneous microcontractions and electrical field-stimulated contractions in isolated strips of rat urinary bladder from normal animals and animals with partial bladder outflow obstruction

Naunyn Schmiedebergs Arch Pharmacol. 2015 Jul;388(7):719-26. doi: 10.1007/s00210-015-1136-z. Epub 2015 Jun 7.

Abstract

Spontaneous microcontractions and electrical field stimulation (EFS)-evoked contractions in isolated rat bladder strips from normal and from 6 weeks partial bladder outflow obstruction (pBOO) animals were studied to identify the potential site of action for the β3-adrenoceptor (AR) agonist mirabegron in detrusor overactivity in rats. For this, effects of the β-AR agonist isoprenaline and mirabegron were tested in presence or absence of selective antagonists for β-AR subtypes, namely CGP-20712A for β1-AR, ICI-118,551 for β2-AR, and L-748,337 for β3-AR. In detrusor strips from both normal and obstructed animals, EFS-induced contractions were weakly affected by isoprenaline and even less so by mirabegron. In contrast, microcontraction activity was more potently reduced by isoprenaline (pIC50 7.3; Emax ±85 %), whereas mirabegron showed a small effect. In pBOO strips, concentration response curves for isoprenaline and mirabegron at inhibition of EFS and spontaneous microcontractions were similar to those in normal strips. Isoprenaline-induced inhibition of microcontractions and EFS was antagonized by the β1-AR antagonist, but not by the β2- and β3-AR antagonists. In the context of β3-AR-mediated bladder functions for mirabegron in other experiments, the current data question a role for effects at spontaneous microcontractions, or neurogenic detrusor stimulation in the mode of action for mirabegron in vivo, since functional bladder effects for mirabegron are reported to occur at much lower concentrations.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Female
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / physiology*
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, beta / metabolism*
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism
  • Urinary Bladder / physiology*
  • Urinary Bladder Neck Obstruction / metabolism
  • Urinary Bladder Neck Obstruction / physiopathology*

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, beta