Downregulation of parathyroid hormone receptors in renal membranes from aged rats.
Downregulation of parathyroid hormone receptors in renal membranes from aged rats.
复制标题
老年大鼠肾膜中甲状旁腺激素受体的下调。
作者：
H. Hanai;D. P. Brennan;L. Cheng;M. Goldman;M. Chorev;Michael A. Levine;B. Sacktor;C. Liang
研究了抑制或减弱老年大鼠肾皮质细胞中甲状旁腺激素 (PTH) 刺激的 Na(+)-Ca2+ 交换活性的机制。通过合成类似物 125I 标记的 [Nle8,18, Tyr34]bPTH-(1-34) 酰胺与膜的结合来定量从成年（6 个月）和老年（24 个月）大鼠制备的基底外侧膜中 PTH 结合位点的数量。在成年和老年大鼠制备的膜中，特异性 PTH 结合位点的最大数量 Bmax 分别为 92.7 +/- 9.3 和 36.7 +/- 6.1 fmol/mg 蛋白质。受体对 PTH 的亲和力不受年龄影响。使用生物素化 bPTH-(1-34) 作为配体，通过配体亲和印迹技术估计的 PTH 结合成分（68 和 70 kDa）的水平在从衰老大鼠中分离的膜中也同样降低。为了检验 PTH 结合位点数量和 PTH 结合成分水平的变化代表对高血清 PTH 水平的适应性反应的假设，对大鼠进行甲状旁腺切除术 (PTX) 并重新检查这些变化。 PTH 结合位点和 PTH 结合成分数量的减少被手术部分或完全抵消。这些发现表明，老年大鼠肾脏中 PTH 刺激的 Na(+)-Ca2+ 交换和腺苷酸环化酶活性的减弱部分是由于基底外侧膜中 PTH 受体的丧失，并且这种缺陷可以通过去除甲状旁腺来部分逆转。
The mechanism of the inhibition or blunting of parathyroid hormone (PTH)-stimulated Na(+)-Ca2+ exchange activity in renal cortical cells from aged rats was examined. The number of PTH binding sites in basolateral membranes prepared from adult (6 mo) and old (24 mo) rats was quantitated by the binding of the synthetic analogue 125I-labeled [Nle8,18, Tyr34]bPTH-(1-34) amide to the membrane. The maximum number of specific PTH binding sites, Bmax, was 92.7 +/- 9.3 and 36.7 +/- 6.1 fmol/mg protein, respectively, in membranes prepared from adult and old rats. The affinity of the receptor to PTH was unaffected with age. The level of PTH binding components (68 and 70 kDa) estimated by a ligand affinity blot technique using biotinylated bPTH-(1-34) as the ligand was similarly reduced in membranes isolated from senescent rats. To test the hypothesis that change in the number of PTH binding sites and level of PTH binding components represented an adaptive response to a high serum PTH level, rats were parathyroidectomized (PTX) and the changes were reexamined. Decreases in the number of PTH binding sites and PTH binding components were either partially or completely negated by the surgery. These findings suggest that the blunting of both the PTH-stimulated Na(+)-Ca2+ exchange and adenylate cyclase activities in the kidneys of aged rats was due, in part, to be loss of PTH receptors in basolateral membranes and that this defect could be partially reversed by removal of the parathyroid gland.