PARATHYROID HORMONE-RELATED PROTEIN IN THE RAT URINARY-BLADDER - A SMOOTH-MUSCLE RELAXANT PRODUCED LOCALLY IN RESPONSE TO MECHANICAL STRETCH
PARATHYROID HORMONE-RELATED PROTEIN IN THE RAT URINARY-BLADDER - A SMOOTH-MUSCLE RELAXANT PRODUCED LOCALLY IN RESPONSE TO MECHANICAL STRETCH
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DOI：
10.1073/pnas.89.12.5326
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发表时间：
1992-06-15
影响因子：
11.1
通讯作者：
THIEDE, MA
中科院分区：
文献类型：
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作者：
YAMAMOTO, M;HARM, SC;THIEDE, MA
妊娠大鼠子宫中的甲状旁腺激素相关蛋白（PTHrP）基因表达依赖于胎儿对子宫的占据。为了进一步检验平滑肌组织中 PTHrP 的合成受机械拉伸调节的假设，我们使用大鼠膀胱作为可膨胀中空器官的模型进行了实验。结果表明，PTHrP mRNA 水平确实会随着膀胱壁的拉伸而发生变化。正常情况下，膀胱中 PTHrP mRNA 水平与尿量（即膀胱扩张程度）相关。当体内膀胱保持排空时，PTHrP mRNA水平逐渐下降。相反，当膀胱因尿液积聚而扩张时，PTHrP mRNA 水平随时间急剧增加。当扩张仅限于膀胱的二分之一时，仅在扩张部分观察到PTHrP mRNA的增加。对扩张的膀胱组织进行的组织化学研究表明平滑肌细胞中存在 PTHrP 免疫反应性。离体器官浴研究用于检查 PTHrP 在平滑肌张力中可能的生理作用。膀胱肌条对外源性 PTHrP 的体外反应取决于膀胱的体内状况。在从体内保持空的膀胱获得的肌肉条中，PTHrP-(1-34)-NH2以剂量依赖性方式松弛卡巴胆碱诱导的收缩，但未能松弛来自具有高内源性PTHrP表达的扩张膀胱的肌肉条的收缩。这些结果和之前在大鼠子宫中的发现表明 PTHrP 在膀胱平滑肌功能中的生理作用。
Parathyroid hormone-related protein (PTHrP) gene expression in the pregnant rat uterus has been shown to be dependent on occupancy of the uterus by the fetus. To further test the hypothesis that the synthesis of PTHrP in smooth muscle tissue is regulated by mechanical stretch, we conducted experiments using the rat urinary bladder as a model of an expansible hollow organ. The results indicate that PTHrP mRNA levels do change in response to the stretch of the bladder wall. Under normal conditions PTHrP mRNA levels in the bladder correlated with the urine volume-namely, the extent of bladder distension. When bladders were maintained empty in vivo, PTHrP mRNA levels decreased gradually. Conversely, when bladders were distended by the accumulation of urine, levels of PTHrP mRNA increased dramatically with time. When distension was limited to one-half of the bladder, the increase in PTHrP mRNA was observed only in the distended portion. Histochemical studies performed on distended bladder tissue indicated the presence of PTHrP immunoreactivity in smooth muscle cells. Isolated organ bath studies were used to examine the possible physiological role of PTHrP in smooth muscle tonicity. In vitro responsiveness of bladder muscle strips to exogenous PTHrP was dependent on the in vivo condition of the bladder. In muscle strips obtained from bladders kept empty in vivo, PTHrP-(1-34)-NH2 relaxed carbachol-induced contraction in a dose-dependent manner but failed to relax the contraction in muscle strips from distended bladders that had high endogenous PTHrP expression. These results and the previous findings in the rat uterus suggest a physiological role of PTHrP in bladder smooth muscle function.