Institut für Physiologie, Medizinische Fakulät Carl Gustav Carus, TU Dresden, Dresden, Germany.
Medizinische Klinik 1, Universitätsklinikum Carl Gustav Carus, TU Dresden, Fetscherstrasse 74, D-01307, Dresden, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2018 Aug;391(8):773-782. doi: 10.1007/s00210-018-1505-5. Epub 2018 Apr 28.
Human proximal and distal ureter tissues were studied to clarify whether the presence of mucosa affects contractile responses. In histological studies, human ureter was compared with urinary bladder (detrusor). Contractions in response to high KCl solution, phenylephrine, and carbachol were measured in intact and mucosa-denuded strips of human ureter. Tissue sections of human bladder and ureter were used for histological staining. Thirty-four percent of the ureter strips contracted spontaneously with highly variable patterns, and this was affected neither by mucosa nor by proximal or distal tissue origin. Upon stimulation with 40 mM KCl, ureter strips exhibited strong phasic and weak tonic contractions. In intact strips, normalized tonic force was lower than in denuded strips, but no consistent effect of mucosa was observed with phasic contractions. Absolute force values of phasic contractions were weaker in proximal than distal ureter strips, but similar when normalized to tissue wet weight. Stimulation with 80 mM KCl enhanced tonic contraction fourfold; phasic contractions occurred rarely. Phenylephrine produced no statistically significant stronger tonic contraction in distal compared with proximal ureter strips; nevertheless, in some strips, pre-existing spontaneous contractions increased. Carbachol did not influence ureter contractions. In the bladder, a suburothelial cell layer stained positive with α-smooth muscle actin (α-SMA)-specific antibodies could be further differentiated with vimentin- and desmin-specific antibodies. α-SMA positive cells were absent in suburothelial ureter tissue. Like in detrusor, the mucosa inhibits KCl-stimulated tonic ureter contractions. The mucosa of detrusor and ureter tissue exhibits distinct staining patterns for α-SMA, vimentin, and desmin. This suggests a different distribution of smooth muscle cells, fibroblasts, and myofibroblasts, which could be a target for pharmacological therapy of pathologic contractile processes.
为了阐明黏膜的存在是否会影响收缩反应,我们对人近段和远段输尿管组织进行了研究。在组织学研究中,我们将人输尿管与尿膀胱(逼尿肌)进行了比较。我们测量了完整和去黏膜的人输尿管条带对高 KCl 溶液、苯肾上腺素和卡巴胆碱的收缩反应。我们使用人膀胱和输尿管的组织切片进行了组织学染色。34%的输尿管条带自发收缩,具有高度可变的模式,这种模式既不受黏膜影响,也不受近段或远段组织起源的影响。在 40 mM KCl 的刺激下,输尿管条带表现出强烈的相收缩和弱的紧张性收缩。在完整的条带中,正常化的紧张力低于去黏膜的条带,但在相收缩中没有观察到黏膜的一致影响。与远段输尿管条带相比,近段输尿管条带的相收缩的绝对力值较弱,但当标准化为组织湿重时,相似。用 80 mM KCl 刺激使紧张性收缩增加了四倍;相收缩很少发生。与近段输尿管条带相比,苯肾上腺素对远段输尿管条带没有产生统计学上更强的紧张性收缩;然而,在一些条带中,预先存在的自发性收缩增加了。卡巴胆碱对输尿管收缩没有影响。在膀胱中,用α-平滑肌肌动蛋白(α-SMA)特异性抗体染色的下尿路上皮细胞层可以进一步用波形蛋白和结蛋白特异性抗体进行区分。在下尿路上皮输尿管组织中没有α-SMA 阳性细胞。与逼尿肌一样,黏膜抑制 KCl 刺激的紧张性输尿管收缩。逼尿肌和输尿管组织的黏膜显示出对 α-SMA、波形蛋白和结蛋白的不同染色模式。这表明平滑肌细胞、成纤维细胞和肌成纤维细胞的分布不同,这可能是病理性收缩过程的药理学治疗的靶点。