Otsuka Atsushi, Shinbo Hitoshi, Matsumoto Rikiya, Kurita Yutaka, Ozono Seiichiro
Department of Urology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):473-81. doi: 10.1007/s00210-008-0274-y. Epub 2008 Mar 1.
We investigated the presence of beta-adrenoceptor subtypes in human urinary bladder urothelium and examined whether beta-adrenoceptors in the urothelium modulate the relaxation responses of isolated human detrusor strips to a beta-adrenoceptor agonist. Expression of beta1-, beta2-, and beta3-adrenoceptor mRNA in urothelium and detrusor smooth muscle was determined by reverse transcription-polymerase chain reaction, and the distribution of beta1-, beta2-, and beta3-adrenoceptors in human urinary bladder urothelium were examined by immunohistochemistry. Paired human longitudinal detrusor strips with and without an intact urothelium were suspended in organ baths to construct concentration-response curves to isoproterenol. The possible involvement of urothelium-derived nitric oxide (NO) in this response was examined in additional experiments with urothelium-intact strips in the presence of NG-nitro-L-arginine methylester (L-NAME). Results confirmed the expression of beta1-, beta2-, and beta3-adrenoceptors in the human urinary bladder urothelium. Further, the presence of the urothelium caused a parallel rightward shift of the concentration-response curve to isoproterenol with a significant reduction in potency (pEC50). L-NAME failed to exert any significant effect on the relaxation response to isoproterenol in the urothelium-intact strips. These results confirm the presence of beta1-, beta2-, and beta3-adrenoceptors in human urinary bladder urothelium. Further, they suggest that urothelial beta-adrenoceptors induce the release of a urothelium-derived factor which inhibits the beta-adrenoceptor agonist-induced relaxation of the human detrusor smooth muscle and that this inhibitory mechanism might not involve NO.
我们研究了人膀胱尿路上皮中β-肾上腺素能受体亚型的存在情况，并检测尿路上皮中的β-肾上腺素能受体是否调节分离的人逼尿肌条对β-肾上腺素能受体激动剂的舒张反应。通过逆转录-聚合酶链反应测定尿路上皮和逼尿肌平滑肌中β1-、β2-和β3-肾上腺素能受体mRNA的表达，并通过免疫组织化学检查人膀胱尿路上皮中β1-、β2-和β3-肾上腺素能受体的分布。将有无完整尿路上皮的人逼尿肌纵行条带置于器官浴槽中，构建对异丙肾上腺素的浓度-反应曲线。在额外的实验中，在存在NG-硝基-L-精氨酸甲酯（L-NAME）的情况下，对有完整尿路上皮的条带进行检测，以研究尿路上皮衍生的一氧化氮（NO）在该反应中的可能作用。结果证实了人膀胱尿路上皮中β1-、β2-和β3-肾上腺素能受体的表达。此外，尿路上皮的存在导致对异丙肾上腺素的浓度-反应曲线平行右移，效力显著降低（pEC50）。L-NAME对有完整尿路上皮条带对异丙肾上腺素的舒张反应未产生任何显著影响。这些结果证实了人膀胱尿路上皮中存在β1-、β2-和β3-肾上腺素能受体。此外，它们表明尿路上皮β-肾上腺素能受体诱导释放一种尿路上皮衍生因子，该因子抑制β-肾上腺素能受体激动剂诱导的人逼尿肌平滑肌舒张，并且这种抑制机制可能不涉及NO。
