AI Article Synopsis
- The study investigates how BRL37344, a β3-adrenergic receptor agonist, reduces nerve-induced contractions in human detrusor smooth muscle.
- BRL37344 significantly lowers the strength and duration of muscle contractions when stimulated, indicating its effectiveness in modulating bladder activity.
- The research highlights the importance of large-conductance Ca(2+)-activated K(+) (BK) channels in this process, suggesting they could be potential targets for treating bladder dysfunction alongside β3-ARs.
Article Abstract
Objective: To investigate the mechanism by which BRL37344, a β3-adrenergic receptor (β3-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 Ca(2+)-activated K(+) (BK) channels in this process.
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).
Results: BRL37344, a β3-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 β3-AR-induced inhibition of human DSM nerve-evoked contractions. We further used atropine, α,β-methylene-ATP, and suramin to separate the cholinergic and purinergic components of human DSM nerve-evoked contractions. We found that the β3-AR agonist, BRL37344, inhibited both components of the EFS-induced (0.5-50 Hz) DSM contractions.
Conclusion: This study supports the concept that β3-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 β3-ARs, BK channels may also represent promising pharmacologic targets in the treatment of urinary bladder dysfunction.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758792 | PMC |
| http://dx.doi.org/10.1016/j.urology.2013.05.027 | DOI Listing |
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