β3-Adrenoceptor-mediated relaxation of rat and human urinary bladder: roles of BKCa channels and Rho kinase

Hana Cernecka*, Kim Kersten, Harm Maarsingh, Carolina R. Elzinga, Igle Jan de Jong, Cees Korstanje, Martin C. Michel, Martina Schmidt

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Previous studies suggest that the large-conductance Ca2+-activated K+ (BKCa) channel and Rho-kinase play major roles in the control of urinary bladder tone. Here, we investigated their involvement in beta-adrenoceptor (AR)-mediated relaxation of rat and human bladder. Concentration-response curves of isoprenaline and mirabegron-induced bladder relaxation were generated against passive tension and KCl- and carbachol-induced tone, in the absence or presence of the BKCa channel inhibitor iberiotoxin (100 nM) or the Rho-kinase inhibitor Y27,632 (1 mu M). Myosin light chain (MLC) phosphorylation was studied by Western blot. In rat, iberiotoxin only slightly altered isoprenaline- and mirabegron-induced relaxation against KCl-induced tone but attenuated relaxation by both agonists against carbachol-induced tone. Y27,632 enhanced isoprenaline- or mirabegron-induced relaxation only against carbachol-induced tone. In humans, iberiotoxin slightly enhanced relaxation by both agonists against carbachol-induced pre-contraction. Y27,632 did not change isoprenaline-induced relaxation but enhanced that by mirabegron. Under passive tension, MLC phosphorylation was markedly reduced by both beta-AR agonists, an effect insensitive to Y27,632. In the presence of carbachol, both beta-AR agonists increased MLC phosphorylation, an effect reduced by Y27,632 only in the presence of 1 mu M carbachol. These results indicate that the extent of BKCa channel and Rho-kinase involvement in relaxation induced by beta-AR agonists depends on pre contractile stimulus and species.

Original languageEnglish
Pages (from-to)749-759
Number of pages11
JournalNaunyn-Schmiedebergs Archives of Pharmacology
Volume388
Issue number7
DOIs
Publication statusPublished - Jul-2015

Keywords

  • BKCa channel
  • Human urinary bladder
  • Mirabegron
  • Rat urinary bladder
  • Rho-kinase
  • CARBACHOL-INDUCED CONTRACTION
  • BETA-ADRENOCEPTOR AGONISTS
  • CA2+-ACTIVATED K+ CHANNELS
  • DETRUSOR SMOOTH-MUSCLE
  • MUSCARINIC RECEPTORS
  • OVERACTIVE BLADDER
  • GUINEA-PIG
  • DIFFERENTIAL REGULATION
  • M-3 RECEPTORS
  • CALCIUM

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