Urothelial Beta-3 Adrenergic Receptors in the Rat Bladder

作者：Kullmann F Aura^*; Downs Thomas R; Artim Debra E; Limberg Brian J; Shah Mansi; Contract Dan; de Groat William C; Rosenbaum Jan S

来源：Neurourology and Urodynamics, 2011, 30(1): 144-150.

DOI：10.1002/nau.20965

• bladder strips
• BRL37344
• cystometry
• immunohistochemistry
• intravesical application
• RT-PCR
• TAK-677
• urethane anesthesia

Aims: To investigate the distribution of beta-3 adrenergic receptors (beta(3)ARs) in the rat bladder and to examine the contribution of urothelial beta(3)ARs 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 beta AR mRNA and beta(3)AR protein were determined using RT-PCR and immmunohistochemistry. Contractile responses to the specific beta(3)AR agonists TAK-677 and BRL37344 were measured in bladder strips with or without the urothelium. The contribution of urothelial beta(3)ARs to the micturition reflex was assessed in continuous cystometry in urethane anesthetized rats using intravesical delivery of beta(3)AR agonists. Results: RT-PCR detected mRNA of all beta ARs in urothelium and smooth muscle. Immunostaining detected beta(3)ARs throughout the urothelium, in the smooth muscle, myofibroblast-like cells, and in the peripheral nerves. Ovariectomy did not change the distribution of beta(3)ARs in any bladder structure. Intravesical administration of TAK-677 and BRL37344 (1-5x10(-4) M) decreased voiding frequency and amplitude of bladder contractions. In bladder strips in vitro both beta(3)AR 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, beta(3)ARs 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.

• 出版日期2011