Urothelial beta-3 adrenergic receptors in the rat bladder

Authors


  • Conflicts of interest: Dr. Kullman: Research grant-Proctor and Gamble; Dr. de Groat: Consultant-Medtronic, Ethicon, Eli Lilly, Takedo, Endo Pharma; Speaker honorarium-Astellas, Medtronic; Equity interests: Pfizer; Dr. Downs: Employee/Director- Proctor and Gamble; Dr. Rosenbaum: Employee/Director-Proctor and Gamble; Dr. Limberg: Equity interests, Employee/Director- Proctor and Gamble.

  • Karl-Erik Andersson led the review process.

Abstract

Aims

To investigate the distribution of beta-3 adrenergic receptors (β3ARs) in the rat bladder and to examine the contribution of urothelial β3ARs to agonist-induced suppression of bladder reflexes and relaxation of smooth muscle.

Methods

Bladder tissue was collected from 8- to 10-month old female SD rats. In some samples, the urothelium was surgically separated from the smooth muscle. The expression and localization of βAR mRNA and β3AR protein were determined using RT-PCR and immmunohistochemistry. Contractile responses to the specific β3AR agonists TAK-677 and BRL37344 were measured in bladder strips with or without the urothelium. The contribution of urothelial β3ARs to the micturition reflex was assessed in continuous cystometry in urethane anesthetized rats using intravesical delivery of β3AR agonists.

Results

RT-PCR detected mRNA of all βARs in urothelium and smooth muscle. Immunostaining detected β3ARs throughout the urothelium, in the smooth muscle, myofibroblast-like cells, and in the peripheral nerves. Ovariectomy did not change the distribution of β3ARs in any bladder structure. Intravesical administration of TAK-677 and BRL37344 (1–5 × 10−4 M) decreased voiding frequency and amplitude of bladder contractions. In bladder strips in vitro both β3AR agonists (10−12 to 10−4 M) relaxed the smooth muscle in a concentration-dependent manner to the same extent in strips with and without the urothelium.

Conclusions

In addition to their presence in bladder smooth muscle, β3ARs are present in the urothelium where their activation may alter reflex voiding via release of factor(s) that act on non-myocyte structures including the afferent and/or efferent nerves to influence bladder contractility. Neurourol. Urodynam. 30:144–150, 2011. © 2010 Wiley-Liss, Inc.

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