Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK.
Neurourol Urodyn. 2010 Sep;29(7):1320-5. doi: 10.1002/nau.20838.
Relaxation of detrusor muscle via β-adrenoceptors may contribute to urine storage during bladder filling. Thus there is increasing interest in β-adrenoceptor agonists as a potential treatment for detrusor overactivity. The role of the urothelium in bladder responses to β-adrenoceptor agonists is not yet clear, although we have shown that these agonists have a greater inhibitory effect on detrusor contraction when the urothelium is intact. The aim was to determine which β-adrenoceptor subtype is involved in this effect.
Paired strips of pig bladder dome mucosa-intact and mucosa-denuded, were mounted in tissue baths. Relaxation responses were obtained to β-adrenoceptor agonists (isoprenaline, dobutamine, salbutamol or BRL37344) in carbachol pre-contracted tissues. Inhibitory effects were studied by obtaining concentration-response curves (CRCs) to carbachol in the presence and absence of β-adrenoceptor agonists. The inhibitory effects of isoprenaline were also studied following incubation with β-adrenoceptor antagonists (propranolol, CGP20712, ICI-118, 551 or SR 59230A; non selected, β(1), β(2) and β(3) selective respectively).
isoprenaline, dobutamine, salbutamol and BRL37344 all relaxed carbachol pre-contracted tissues and responses were similar in intact and denuded strips. In inhibition experiments, β-adrenoceptor agonists caused rightward shifts of carbachol CRCs. In intact strips the shift was greater with isoprenaline and BRL37344, but not with dobutamine or salbutamol. This increased shift was still observed in tissues pre-incubated with propranolo, CGP20712 and ICI-118, 551, but not with SR 59230A.
β(3)-adrenoceptors are involved in mediating inhibitory effects of β-adrenoceptor agonists on detrusor contractions via the urothelium in pig bladder dome.
通过β-肾上腺素能受体使逼尿肌松弛可能有助于膀胱充盈时的尿液储存。因此，β-肾上腺素能受体激动剂作为治疗逼尿肌过度活动的潜在药物越来越受到关注。尽管我们已经表明，在尿路上皮完整的情况下，这些激动剂对逼尿肌收缩的抑制作用更大，但尿路上皮在膀胱对β-肾上腺素能受体激动剂反应中的作用尚不清楚。目的是确定哪种β-肾上腺素能受体亚型与此效应有关。
将猪膀胱穹窿粘膜完整和粘膜剥除的成对条带安装在组织浴中。在乙酰胆碱预收缩的组织中，用β-肾上腺素能受体激动剂（异丙肾上腺素、多巴酚丁胺、沙丁胺醇或 BRL37344）获得松弛反应。通过在存在和不存在β-肾上腺素能受体激动剂的情况下获得对乙酰胆碱的浓度-反应曲线（CRC）来研究抑制作用。还研究了异丙肾上腺素在与β-肾上腺素能受体拮抗剂（普萘洛尔、CGP20712、ICI-118、551 或 SR 59230A；非选择性、β(1)、β(2)和β(3)选择性）孵育后对异丙肾上腺素的抑制作用。
异丙肾上腺素、多巴酚丁胺、沙丁胺醇和 BRL37344 均可松弛乙酰胆碱预收缩的组织，完整和剥脱条带的反应相似。在抑制实验中，β-肾上腺素能受体激动剂导致乙酰胆碱 CRC 发生右移。在完整的条带中，异丙肾上腺素和 BRL37344 的移动更大，但多巴酚丁胺或沙丁胺醇则不然。这种增加的移动仍然可以在预先用普萘洛尔、CGP20712 和 ICI-118、551 孵育的组织中观察到，但在 SR 59230A 中则不然。
β(3)-肾上腺素能受体参与介导猪膀胱穹窿中尿路上皮的β-肾上腺素能受体激动剂对逼尿肌收缩的抑制作用。
