Itoh K, Hara T
Department of Molecular Cardiology, Center for Adult Diseases, Osaka, Japan.
Biochem Int. 1992 Aug;27(4):633-9.
Renal cortex homogenates from aged (greater than 5 y) rabbits showed decreased specific activities of brush border membrane enzymes compared to those from control young (6 m) rabbits but the specific enzyme activities of basolateral membrane, endoplasmic reticulum and mitochondria did not differ between the two groups. The stimulatory effects of parathyroid hormone (PTH) on the Ca(2+)-pump enzyme [(Ca(2+)+Mg2+)-ATPase] activity in kidney cortex homogenates were markedly less in aged rabbits, but the effect of cAMP on this enzyme activity was similar. Moreover, the production of cAMP induced by PTH was markedly less in the renal cortex homogenates from aged rabbits. From these results, we have proposed the following mechanism; aging--decrease in the response of cAMP to PTH in renal cortex--decrease in the stimulatory effect of PTH via cAMP on the Ca(2+)-pump enzyme--decreased reabsorption of Ca2+ from ureter--increased urinary Ca2+ secretion. This pathway may contribute to the worsening of senile osteoporosis.
与对照幼兔(6个月)相比,老年(大于5岁)兔肾皮质匀浆显示刷状缘膜酶的比活性降低,但两组之间基底外侧膜、内质网和线粒体的比酶活性没有差异。甲状旁腺激素(PTH)对肾皮质匀浆中钙泵酶[(Ca²⁺+Mg²⁺)-ATP酶]活性的刺激作用在老年兔中明显较弱,但cAMP对该酶活性的作用相似。此外,老年兔肾皮质匀浆中PTH诱导的cAMP产生明显较少。根据这些结果,我们提出了以下机制;衰老——肾皮质中cAMP对PTH的反应降低——PTH通过cAMP对钙泵酶的刺激作用降低——输尿管对Ca²⁺的重吸收减少——尿Ca²⁺分泌增加。这条途径可能导致老年性骨质疏松症的恶化。