Determination of controlling factor of detrusor contraction in urothelium and the role of Rho Kinase

尿路上皮逼尿肌收缩控制因子的测定及Rho激酶的作用

• 批准号: 18591770
• 负责人: YAMANISHI Tomonori
• 金额: $ 2.53万
• 依托单位: Dokkyo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591770/
• 关键词: bladder; urothelium; muscarinic; β-adrenoceotor; Y 27632; fasudil; Rho; Rho-kinase; Y27632; Fasudil; Rho活性; カルバコール; 平滑筋; サブタイプ; 下部尿路閉塞

The mRNA and protein expression of muscarinic receptor subtypes, adorenoceptor subtypes as well as RhoA/Rho kinase and its activity were investigated by radioligand binding experiments, realtime RT-PCR, Western blotting and immunohistochemistry in urothelium and detrusor muscle of the pig and human. We have hind that M2 muscarinic, receptor subtypes were predominantly present in both urothelium and detrusor of the pig bladder. However M3 muscarinic receptor subtypes were more hind in urothelium and smooth muscle of the human bladder Among β-receptor subtypes, β3-adrenoceptor were predominantly found in detrusor muscle of the pig and human.The expression of RhoA was more hind in the urothelium than in the smooth mule of the bladder in pig and human. The activity of RhoA determined by Western blotting were also greater in the urothelium than in the smooth muscle of the pig bladder.In functional studies, the responses to Y-27632 and fasudil, Rho-kinase inhibitors, were examined in bladder … More tissue strips with or without urothelium. Mansion decrease after administration of Y-27632 (InM-100μM) was significantly greater in tissues with intact urothelium than in tissues without urothelium, after pre-contraction with KCl (decrease by 52.0±4.6% vs 28±6.8%, respectively; p=0.0088) or with carbachol (decrease by 53.1±7.2% vs 30.6±5.81%, respectively; p=0.0035). Maximum contraction on CRC to carbachol was reduced significantly alter administration of 3, 10 and 30μM Y-27632 (to 72.2±6.8%, 43.9±7.1%, and 25.015.5%, respectively of the control value) in strips with intact urothelium (n=36), but was reduced only at 10 and 30 μM (to 66.7±825% and 85.6±2.6%, respectively) in tissues without urothelium Inhibitory effect of Y-27632 (3- 30μM) on the response to electrical field stimulation at 20Hz and 50 Hz was also greater in tissue strips with intact urothelium than in tissues without urothelium.In conclusion, the expression of RhoA mRNA and activated RhoA were greater in urothelium than in bladder smooth muscle. Y-27632 showed a stronger inhibitory effect on tissue preparations with intact urothelium than co those without urothelium. Less

采用放射配基结合实验、实时定量RT-PCR、Western blotting和免疫组织化学方法，研究了猪和人尿路上皮和逼尿肌中M受体亚型、受体亚型和RhoA/Rho激酶的基因和蛋白表达及其活性。我们发现M2受体亚型主要存在于猪膀胱的尿路上皮和逼尿肌中。在β受体亚型中，M3受体亚型在人膀胱的尿路上皮和平滑肌中的表达较晚，β3受体主要在猪和人的逼尿肌中表达，在猪和人的膀胱中的表达比在膀胱中的表达更晚。在功能研究中，研究了膀胱…对Y-27632和法舒地尔的反应有或没有尿路上皮的更多组织条。在有完整尿路上皮的组织中，Y-27632(INM-27632μM)在用氯化钾或卡巴胆碱预收缩后(分别下降52.0±4.6%和28±6.8%；p=0.0088)显著大于无尿路上皮的组织(分别下降53.1±7.2%和30.6±5.81%；p=0.0035)。在36条尿路上皮完整的组织条中，3、10和30μ的M Y-27632对卡巴胆碱的最大收缩作用显著降低(分别为对照的72.2±6.8%、43.9±7.1%和25.015.5%)，而在无尿路上皮的组织中，Y-27632(3-30μM)对电场刺激的抑制作用仅在10μM时才减少(分别为66.7±825%和85.6±2.6%)。结论：在有完整尿路上皮的组织条中，Y-27632对20 Hz和50 Hz电场刺激的抑制作用也大于无尿路上皮组织。RhoA mRNA和活化的RhoA在尿路上皮中的表达强于在膀胱平滑肌中的表达。Y-27632对尿路上皮完整的组织制剂的抑制作用强于无尿路上皮的组织制剂。较少

项目成果

Present advances in clinical aspects of neurogenic bladder(Symposium:The Neurogeaic Bladder:Where are we now?)

神经源性膀胱临床方面的最新进展（研讨会：神经源性膀胱：我们现在在哪里？）

• 发表时间: 2007
• 作者: Yamanishi;T.;et. al.;Yamanishi T
• 通讯作者: Yamanishi T

Lower urinary tract dysfunction after radical bysterectomy

根治性子宫切除术后下尿路功能障碍

• 发表时间: 2007
• 作者: Yamanishi T;et. al.
• 通讯作者: et. al.

Urodvnamic effects of silodosin,a new alphalAlpba- adrenoceptor selective antagonist,for the treatment of benign prostatic liyperplasia

新型α1Alpba-肾上腺素受体选择性拮抗剂西洛多辛治疗良性前列腺增生症的尿动力学作用

• 发表时间: 2006
• 作者: Yamanishi T;et. al.
• 通讯作者: et. al.

Randomized, double-blind, sham-controlled evaluation of the effect of functional continuous magnetic stimulation in patients with urgency incontinence

• DOI: 10.1002/nau.20423
• 发表时间: 2007-01-01
• 期刊: NEUROUROLOGY AND URODYNAMICS
• 影响因子: 2
• 作者: Suzuki, Tsuneki;Yasuda, Kosaku;Ohkawa, Hiromi
• 通讯作者: Ohkawa, Hiromi

Urinary dysfunction and autonomic control in amyloid neuropathy

淀粉样神经病的排尿功能障碍和自主控制

• 发表时间: 2006
• 期刊: Clin Auton Res 16
• 作者: Ito T;Sakakibara R;Yamamoto T;Uchiyama T;Liu Z;Asahina M;Higashi M;Arai K;Ito S;Awa Y;Yamamoto K;Kinou M;Yamanishi T;Hattori T
• 通讯作者: Hattori T