Desensitization to parathyroid hormone in renal cells from aged rats is associated with alterations in G-protein activity.
Desensitization to parathyroid hormone in renal cells from aged rats is associated with alterations in G-protein activity.
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老年大鼠肾细胞对甲状旁腺激素的脱敏与 G 蛋白活性的改变有关。
DOI：
--
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发表时间：
1989
影响因子：
15.9
通讯作者：
B. Sacktor
中科院分区：
文献类型：
--
作者：
H. Hanai;C. Liang;L. Cheng;B. Sacktor
甲状旁腺激素（PTH）刺激的Na+/Ca 2+交换活性，但不毛喉素敏感的Na+依赖的Ca 2+流出，钝化在老年大鼠肾皮质细胞。PTH敏感的腺苷酸环化酶的活性在衰老大鼠肾膜也下降，但毛喉素刺激的活动没有改变。此外，霍乱毒素和百日咳毒素刺激的Na+-依赖的Ca 2+流出和cAMP的形成钝化的细胞从老年动物。此外，来自老年大鼠的细胞具有减少的Gs-alpha和Gi-alpha蛋白，如通过ADP-核糖基化检测到的。这些发现将与涉及G蛋白的年龄相关的异源脱敏的提议一致。老年大鼠血清中iPTH浓度升高，表明老年大鼠对PTH的脱敏代表了对激素长期刺激的适应性反应。这一假设得到了以下结果的支持：老年大鼠细胞中PTH敏感性Na+/Ca 2+交换活性、cAMP形成和腺苷酸环化酶活性的减弱可以通过甲状旁腺切除术逆转。在来自老年大鼠的细胞中发现的霍乱毒素催化的ADP-核糖基化的Gs-α和百日咳毒素催化的ADP-核糖基化的Gi-α中的标记减少也在很大程度上被手术否定。总之，结果表明，年龄相关的钝化反应的肾细胞PTH与G-蛋白功能的缺陷，这种改变可以通过去除甲状旁腺逆转。
Parathyroid hormone (PTH)-stimulated Na+/Ca2+ exchange activity, but not forskolin-sensitive Na+-dependent Ca2+ efflux, was blunted in renal cortical cells from aged rats. PTH-sensitive adenylate cyclase activity in renal membranes from senescent rats also declined, but forskolin-stimulated activity did not change. In addition, cholera toxin- and pertussis toxin-stimulated Na+-dependent Ca2+ efflux and cAMP formation were blunted in cells from aged animals. Further, cells from aged rats had decreased Gs-alpha and Gi-alpha proteins, as detected by ADP-ribosylation. These findings would be consistent with the proposal of an age-associated heterologous desensitization that involved the G-proteins. Serum concentrations of iPTH were increased in the old rat, suggesting that the desensitization to PTH in the aging rat represented an adaptive response to prolonged stimulation by the hormone. This hypothesis was supported by the findings that the attenuated PTH-sensitive Na+/Ca2+ exchange activity, cAMP formation, and adenylate cyclase activity in cells from old rats could be reversed by parathyroidectomy. The decreased label in cholera toxin-catalyzed ADP-ribosylated Gs-alpha and pertussis toxin catalyzed ADP-ribosylated Gi-alpha found in cells from aged rats was also largely negated by the surgery. In conclusion, the results suggest that the age-related blunting in the responses of renal cells to PTH was associated with a deficit in G-protein function and that this alteration could be reversed by removal of the parathyroid gland.
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激素受体-腺苷酸环化酶偶联蛋白的缺乏：假性甲状旁腺功能减退症激素抵抗的基础。
DOI：
10.1152/ajpendo.1982.243.1.e37
发表时间：
1982
期刊：
The American journal of physiology
影响因子：
--
作者：
Spiegel,AM;Levine,MA;Aurbach,GD;DownsJr,RW;Marx,SJ;Lasker,RD;Moses,AM;Breslau,NA
通讯作者：
Breslau,NA
饮食引起的甲状旁腺功能亢进症对犬肾甲状旁腺激素-受体-腺苷酸环化酶系统的影响。
DOI：
10.1172/jci110990
发表时间：
1983
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Tamayo,J;Bellorin-Font,E;Martin,KJ
通讯作者：
Martin,KJ
DOI：
10.1016/s0021-9258(18)67553-2
发表时间：
1986-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. Robishaw;M. Smigel;A. Gilman
通讯作者：
J. Robishaw;M. Smigel;A. Gilman
儿茶酚胺刺激的腺苷酸环化酶的分化依赖性表达。
DOI：
--
发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lai,E;Rosen,OM;Rubin,CS
通讯作者：
Rubin,CS
培养的鸡肾细胞对甲状旁腺激素的同源脱敏。
影响因子：
4.8
作者：
Henry,HL;Cunningham,NS;NolandJr,TA
通讯作者：
NolandJr,TA