科研之友
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摘要
OBJECTIVE To investigate the mechanism by which BRL37344, a beta 3-adrenergic receptor (beta 3-ARs) agonist, facilitates the inhibition of nerve-evoked contractions in human detrusor smooth muscle (DSM) isolated strips and to identify the role of large-conductance Ca2+-activated K+ (BK) channels in this process. %26lt;br%26gt;METHODS Human DSM specimens were obtained from open bladder surgeries on patients without preoperative history of overactive bladder symptoms. Isometric DSM tension recordings were conducted using force-displacement transducers and thermostatically controlled tissue baths. Nerve-evoked contractions were generated by electrical field stimulation (EFS). %26lt;br%26gt;RESULTS BRL37344, a beta 3-AR agonist, significantly decreased the amplitude, muscle force, and duration of the DSM contractions induced by 20 Hz EFS, in a concentration-dependent manner. This BRL37344-mediated inhibition of the amplitude and muscle force of the nerve-evoked DSM contraction was significantly reduced by iberiotoxin, a highly selective inhibitor of the BK channel, revealing a role for BK channels in the beta 3-AR-induced inhibition of human DSM nerve-evoked contractions. We further used atropine, alpha,beta-methylene-ATP, and suramin to separate the cholinergic and purinergic components of human DSM nerve-evoked contractions. We found that the beta 3-AR agonist, BRL37344, inhibited both components of the EFS-induced (0.5-50 Hz) DSM contractions. %26lt;br%26gt;CONCLUSION This study supports the concept that beta 3-AR agonists inhibit nerve-evoked contractions in human DSM. We have further revealed that BK channels play a critical role in BRL37344-mediated relaxation of nerve-evoked contractions in human DSM. The study suggests that in addition to beta 3-ARs, BK channels may also represent promising pharmacologic targets in the treatment of urinary bladder dysfunction.
- 出版日期2013-9
