Shapiro E, Tang R, Rosenthal E, Lepor H
Department of Urology, Medical College of Wisconsin, Milwaukee.
J Urol. 1991 Aug;146(2 ( Pt 2)):520-3. doi: 10.1016/s0022-5347(17)37842-4.
The present study was designed to compare the binding and functional properties of calcium channel receptors in normal and myelodysplastic bladders. Normal bladders were obtained from children with vesicoureteral reflux undergoing ureteral reimplantation. Myelodysplastic bladder specimens were obtained from patients undergoing bladder augmentation. The functional studies included agonist (calcium chloride) dose response experiments and the determination of apparent antagonist dissociation constants for various calcium channel antagonists. The receptor binding studies were performed using the ligand (+)-3H-PN200-110 (specific activity 86.6 Ci./mmol.). The mean maximal response of myelodysplastic bladders to calcium ions was 31% less than normal bladders (p greater than 0.05). The mean EC50 for calcium mediated isometric tension and the mean -log antagonist dissociation constant values of nifedipine, diltiazem and verapamil were similar in normal and myelodysplastic bladders. The radioligand receptor binding studies demonstrated that the equilibrium dissociation constant of (+)-3H-PN200-110 in myelodysplastic bladders was 4-fold greater than in normal bladders. The density of dihydropyridine binding sites in myelodysplastic and normal bladders was similar. Our study demonstrated that the pathophysiology of the poorly compliant hyperreflexic bladder is not related to up regulation of dihydropyridine calcium channel receptors or alterations in the response of detrusor muscle to calcium ions. The relative abundance of calcium channel receptors in the normal and myelodysplastic bladders, and the regulation of detrusor contraction by calcium ions suggest that calcium channel receptors have a meaningful role in detrusor function.
本研究旨在比较正常膀胱和骨髓发育不良膀胱中钙通道受体的结合特性与功能特性。正常膀胱取自接受输尿管再植术的膀胱输尿管反流患儿。骨髓发育不良膀胱标本取自接受膀胱扩大术的患者。功能研究包括激动剂（氯化钙）剂量反应实验以及测定各种钙通道拮抗剂的表观拮抗剂解离常数。受体结合研究使用配体（+）-3H-PN200-110（比活度86.6 Ci./mmol.）进行。骨髓发育不良膀胱对钙离子的平均最大反应比正常膀胱低31%（p>0.05）。正常膀胱和骨髓发育不良膀胱中钙介导的等长张力的平均EC50以及硝苯地平、地尔硫䓬和维拉帕米的平均-log拮抗剂解离常数值相似。放射性配体受体结合研究表明，骨髓发育不良膀胱中（+）-3H-PN200-110的平衡解离常数比正常膀胱大4倍。骨髓发育不良膀胱和正常膀胱中二氢吡啶结合位点的密度相似。我们的研究表明，顺应性差的反射亢进膀胱的病理生理学与二氢吡啶钙通道受体的上调或逼尿肌对钙离子反应的改变无关。正常膀胱和骨髓发育不良膀胱中钙通道受体的相对丰度以及钙离子对逼尿肌收缩的调节表明，钙通道受体在逼尿肌功能中具有重要作用。
