title: β3-Adrenoceptor-mediated relaxation of rat and human urinary bladder: roles of BKCa channels and Rho kinase.
abstract: Previous studies suggest that the large-conductance Ca(2+)-activated K(+) (BKCa) channel and Rho-kinase play major roles in the control of urinary bladder tone. Here, we investigated their involvement in β-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 μM). 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 β-AR agonists, an effect insensitive to Y27,632. In the presence of carbachol, both β-AR agonists increased MLC phosphorylation, an effect reduced by Y27,632 only in the presence of 1 μM carbachol. These results indicate that the extent of BKCa channel and Rho-kinase involvement in relaxation induced by β-AR agonists depends on pre contractile stimulus and species.
authors.affiliation: Department of Molecular Pharmacology, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands, hana.cernecka@mdc-berlin.de.
authors.forename: Hana
authors.initials: H
authors.lastname: Cernecka
authors.forename: Kim
authors.initials: K
authors.lastname: Kersten
authors.forename: Harm
authors.initials: H
authors.lastname: Maarsingh
authors.forename: Carolina R
authors.initials: CR
authors.lastname: Elzinga
authors.forename: Igle Jan
authors.initials: IJ
authors.lastname: de Jong
authors.forename: Cees
authors.initials: C
authors.lastname: Korstanje
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
authors.forename: Martina
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000577:Amides / Q000494:pharmacology; D000818:Animals; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D017208:Rats, Wistar; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D013045:Species Specificity; D013844:Thiazoles / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D000577:Amides; C494841:KCNMA1 protein, human; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D010455:Peptides; D011725:Pyridines; D022702:Receptors, Adrenergic, beta-3; D013844:Thiazoles; C108830:Y 27632; C064719:iberiotoxin; D054460:rho-Associated Kinases; C520025:mirabegron