The actions of isoprenaline and mirabegron in the isolated whole rat and guinea pig bladder.
β3-adrenoceptor agonists influence overactive bladder in humans and animal models. However, data is emerging that the mode of action of these drugs is complex. The present study explored the actions of the β3-adrenergic agonist mirabegron and the non-selective agonist isoprenaline on the contractile systems in the rat and guinea pig bladder. Intravesical pressure was measured in isolated whole bladders from female adult animals. In both species spontaneous contractile activity was observed. The muscarinic agonist arecaidine produced complex responses consisting of an initial transient pressure rise followed by complex phasic activity. Three contractile elements were identified: intrinsic micro-contractile activity, initial transient response and steady state phasic activity. The intrinsic and steady state activity could be further divided into a baseline pressure with superimposed phasic activity. The effects of isoprenaline and mirabegron were investigated on these elements. In the rat, the micro-contractile activity could be completely inhibited by isoprenaline (full agonist). The arecaidine-induced initial and steady state baseline pressures were partially reduced, while the phasic activity was little affected. In the guinea pig, both the arecaidine-induced baseline pressure and the phasic activity were affected by isoprenaline. Mirabegron didn't produce significant inhibitory effects in any of the contractile elements in either species. These results show that complex contractile systems operate in the rat and guinea pig bladder that can be modulated by β1/β2-adrenoceptor mechanisms. No evidence was obtained for any β3-dependent regulation of contraction. These data support similar data in humans. Therefore the primary site of therapeutic action of β3-adrenergic agonists remains unknown.
Department of Urology, Antwerp University Hospital and University of Antwerp, Faculty of Medicine, Antwerp, Belgium. Electronic address: sarapersyn@hotmail.com.
Sara
S
Persyn
Department of Urology, Antwerp University Hospital and University of Antwerp, Faculty of Medicine, Antwerp, Belgium. Electronic address: stefan.dewachter@uantwerpen.be.
Stefan
S
De Wachter
Department of Urology, Antwerp University Hospital and University of Antwerp, Faculty of Medicine, Antwerp, Belgium. Electronic address: wyndaelejj@skynet.be.
Jean-Jacques
JJ
Wyndaele
Uro-physiology Research Group, The Dental and Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, England, United Kingdom. Electronic address: j.e.eastham@newcastle.ac.uk.
Jane
J
Eastham
Uro-physiology Research Group, The Dental and Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, England, United Kingdom. Electronic address: james.innes.gillespie@gmail.com.
James
J
Gillespie
D000083:Acetanilides / Q000494:pharmacology*; D000818:Animals; D001115:Arecoline / Q000031:analogs & derivatives / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques / Q000379:methods; D007545:Isoproterenol / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects*
D000083:Acetanilides; D018721:Muscarinic Agonists; D013844:Thiazoles; C015688:arecaidine; D001115:Arecoline; D002217:Carbachol; D007545:Isoproterenol; C520025:mirabegron
Guinea pig; Isoprenaline; Mirabegron; Phasic activity; Rat; Urinary bladder