Rohrmann D, Zderic S A, Wein A J, Levin R M
Department of Urology, Klinikum der Rheinisch-Westfälischen, Technischen Hochschule, Aachen, Germany.
Pharmacology. 1996 Feb;52(2):119-24. doi: 10.1159/000139375.
Excitation-contraction coupling is achieved by translocation of calcium from the extracellular space as well as by the release of calcium from intracellular stores. Thapsigargin has been shown to selectively block the sarcoplasmic Ca-ATPase, thereby preventing the reuptake of calcium into intracellular stores and the participation of these calcium storage sites in the contractile response to stimulation. The current study determined the effect of thapsigargin on the contractile response to field stimulation, bethanechol, and KCl in control rabbit bladders and bladders obtained from rabbits subjected to partial outlet obstruction. Partial bladder outlet obstruction resulted in a marked increase in bladder mass and in significant decreases in the contractile response to field stimulation, bethanechol, and KCl. Thapsigargin (5-40 microM) had no effect on the contractile responses of bladder strips isolated from control rabbits to field stimulation, bethanechol, or KCl. However, bladder strips isolated from obstructed rabbits showed a significant concentration-dependent decrease in the contractile response to field stimulation in the presence of thapsigargin. Thapsigargin had no effect on the contractile responses of bladder strips isolated from obstructed rabbits to either bethanechol or KCl. In general, the data described in this study support our current hypothesis: as smooth muscle cells enlarge (hypertrophy) and the cell volume increases, there is an increased dependence on the release of intracellular calcium from the sarcoplasmic reticulum to mediate the contractile response to field stimulation.
兴奋-收缩偶联是通过细胞外空间钙的转运以及细胞内钙库中钙的释放来实现的。毒胡萝卜素已被证明能选择性地阻断肌浆网钙ATP酶，从而阻止钙重新摄取到细胞内钙库以及这些钙储存位点参与对刺激的收缩反应。本研究确定了毒胡萝卜素对对照兔膀胱以及部分出口梗阻兔膀胱对电场刺激、氨甲酰甲胆碱和氯化钾的收缩反应的影响。部分膀胱出口梗阻导致膀胱重量显著增加，以及对电场刺激、氨甲酰甲胆碱和氯化钾的收缩反应显著降低。毒胡萝卜素（5 - 40微摩尔）对从对照兔分离的膀胱条对电场刺激、氨甲酰甲胆碱或氯化钾的收缩反应没有影响。然而，从梗阻兔分离的膀胱条在毒胡萝卜素存在下对电场刺激的收缩反应呈现出显著的浓度依赖性降低。毒胡萝卜素对从梗阻兔分离的膀胱条对氨甲酰甲胆碱或氯化钾的收缩反应没有影响。总体而言，本研究中描述的数据支持我们目前的假设：随着平滑肌细胞增大（肥大）且细胞体积增加，对从肌浆网释放细胞内钙以介导对电场刺激的收缩反应的依赖性增加。
