Liang C T, Hanai H, Ishida M, Cheng L, Sacktor B
Laboratory of Biological Chemistry, National Institute on Aging National Institutes of Health, Baltimore, MD 21224.
Environ Health Perspect. 1990 Mar;84:137-40. doi: 10.1289/ehp.9084137.
Parathyroid hormone, when incubated with renal cells acting in vivo and in vitro, increased Na+/Ca2+ exchange activity. The effect of parathyroid hormone was specific for biologically active analogs and could be mimicked by cAMP and forskolin. Parathyroid hormone-sensitive Na+/Ca2+ exchange activity was markedly blunted in cells from senescent rats. Parathyroid hormone-stimulated adenylate cyclase was also decreased in aging. In contrast, forskolin-stimulated Na(+)-dependent Ca2+ efflux and adenylate cyclase did not change with senescence. Decrease of PTH binding sites was observed in cells from old rats. Further, cells from 24-month-old rats had decreased Gs and Gi proteins, as detected by ADP-ribosylation. Since serum iPTH level was elevated in the old rat and could contribute to the desensitization to PTH, we tested this hypothesis by comparing sham-operated and PTX animals. The decreases in PTH-sensitive Na+/Ca2+ exchange activity and adenylate cyclase activity in cells from 24-month-old rats could be completely negated by parathyroidectomy. Decrease in PTH binding sites and contents of Gs and Gi in cells from aged-rats was partially negated by the surgery. In conclusion, our results suggested that the age related blunting in responses of renal cells to PTH was due, at least in part, to the elevated serum iPTH level in old rats.
甲状旁腺激素在体内和体外与肾细胞共同孵育时，会增加钠钙交换活性。甲状旁腺激素的作用对生物活性类似物具有特异性，并且可被环磷酸腺苷（cAMP）和福斯可林模拟。衰老大鼠细胞中对甲状旁腺激素敏感的钠钙交换活性明显减弱。衰老过程中，甲状旁腺激素刺激的腺苷酸环化酶也减少。相比之下，福斯可林刺激的钠依赖钙外流和腺苷酸环化酶不会随衰老而改变。在老年大鼠的细胞中观察到甲状旁腺激素结合位点减少。此外，通过ADP-核糖基化检测发现，24月龄大鼠的细胞中Gs和Gi蛋白减少。由于老年大鼠血清中免疫反应性甲状旁腺激素（iPTH）水平升高，可能导致对甲状旁腺激素脱敏，我们通过比较假手术和甲状旁腺切除的动物来验证这一假设。24月龄大鼠细胞中对甲状旁腺激素敏感的钠钙交换活性和腺苷酸环化酶活性的降低可被甲状旁腺切除术完全消除。老年大鼠细胞中甲状旁腺激素结合位点以及Gs和Gi含量的降低可被该手术部分消除。总之，我们的结果表明，肾细胞对甲状旁腺激素反应的年龄相关减弱至少部分归因于老年大鼠血清iPTH水平升高。
