Urothelial/Lamina Propria Spontaneous Activity and the Role of M3 Muscarinic Receptors in Mediating Rate Responses to Stretch and Carbachol
Urothelial/Lamina Propria Spontaneous Activity and the Role of M3 Muscarinic Receptors in Mediating Rate Responses to Stretch and Carbachol
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DOI：
10.1016/j.urology.2011.08.039
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发表时间：
2011-12-01
期刊：
影响因子：
2.1
通讯作者：
Chess-Williams, Russ
中科院分区：
文献类型：
--
作者：
Moro, Christian;Uchiyama, Jumpei;Chess-Williams, Russ
目的研究组织牵张和M受体刺激对猪尿道鞘/固有层自发活动的影响，并鉴定介导这些反应的特异性受体亚型。毒蕈碱受体亚型选择性拮抗剂被用来确定影响收缩率的反应，拉伸和刺激carbachol.Results孤立条urothoracic固有层自发收缩（3.7周期/分钟），不受河豚毒素，N ω-硝基-L-精氨酸，或吲哚美辛的受体。卡巴胆碱（1 μ M）使这些组织条的自发收缩率增加122% ± 27%（P <0.001）。这些反应在M3选择性毒蕈碱拮抗剂4-二苯基乙酰氧基-N-甲基哌啶甲碘化物（10-30 nM）的存在下被显著抑制，但不受M1选择性拮抗剂哌仑西平（30-100 nM）或M2选择性拮抗剂甲氧曲明（0.1-1 μ M）的影响。拉伸的组织也引起了自发收缩率的增加，这些反应被废除阿托品（1 μ M）和低浓度的4-二苯基乙酰氧基-N-甲基哌啶甲碘（10 nM）。达非那新，奥昔布宁，托特罗定，索利那新（1 μ M）都显着抑制卡巴胆碱（1 μ M）的频率响应。结论与固有层的尿路上皮表现出自发的收缩活动，在拉伸过程中增加。该机制似乎涉及作用于M3毒蕈碱受体的内源性乙酰胆碱释放。临床上使用的抗胆碱能药物抑制这些组织的反应，这种机制可能代表了这些药物在治疗膀胱过度活动中的额外作用部位。泌尿学78：1442。e9-1442。e15，2011年。(C)2011 Elsevier Inc.
OBJECTIVE To investigate the effects of tissue stretch and muscarinic receptor stimulation on the spontaneous activity of the urothelium/ lamina propria and identify the specific receptor subtype mediating these responses.METHODS Isolated strips of porcine urothelium with lamina propria were set up for in vitro recording of contractile activity. Muscarinic receptor subtype-selective antagonists were used to identify the receptors influencing the contractile rate responses to stretch and stimulation with carbachol.RESULTS Isolated strips of urothelium with lamina propria developed spontaneous contractions (3.7 cycles/min) that were unaffected by tetrodotoxin, N omega-nitro-L-arginine, or indomethacin. Carbachol (1 mu M) increased the spontaneous contractile rate of these tissue strips by 122% +/- 27% (P < .001). These responses were significantly depressed in the presence of the M3-selective muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (10-30 nM) but were not affected by the M1-selective antagonist pirenzepine (30-100 nM) or the M2-selective antagonist methoctramine (0.1-1 mu M). Stretching of the tissue also caused an increase in the spontaneous contractile rate, and these responses were abolished by atropine (1 mu M) and low concentrations of 4-diphenylacetoxy-N-methylpiperidine methiodide (10 nM). Darifenacin, oxybutynin, tolterodine, and solifenacin (1 mu M) all significantly depressed the frequency responses to carbachol (1 mu M).CONCLUSION The urothelium with the lamina propria exhibits a spontaneous contractile activity that is increased during stretch. The mechanism appears to involve endogenous acetylcholine release acting on M3 muscarinic receptors. Anticholinergic drugs used clinically depress the responses of these tissues, and this mechanism might represent an additional site of action for these drugs in the treatment of bladder overactivity. UROLOGY 78: 1442. e9-1442. e15, 2011. (C) 2011 Elsevier Inc.