Takamoto S, Seino Y, Sacktor B, Liang C T
Laboratory of Biological Chemistry, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
Biochim Biophys Acta. 1990 Apr 23;1034(1):22-8. doi: 10.1016/0304-4165(90)90148-p.
We confirmed our previous observation that duodenal Ca2+ absorption and serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels declined concurrently in old (24 months old) rats as compared to young (6 months old) rats. It is well known that 1,25-dihydroxyvitamin D-3 (1,25-(OH)2D3) expresses its action after binding to specific receptor molecules. In this paper, we compared certain properties of rat duodenal 1,25-(OH)2D3 receptors from old and young animals. Receptor preparations were incubated with [3H]1,25-(OH)2D3 to quantitate the number of unoccupied and total receptor sites and showed that total and unoccupied receptor sites decreased by 22 and 16%, respectively in old rats. Endogenously occupied sites were reduced by 43% in duodenum of the old rat and, consequently, the percentage of receptor occupancy also declined. Age did not affect the dissociation constant (KD) of 1,25-(OH)2D3 from the receptor; the sedimentation coefficient (3.3 S) of the tritiated 1,25-(OH)2D3-receptor complex in sucrose density centrifugation; or its affinity for DNA. The data are consistent with the hypothesis that the age-related decline in Ca2+ absorption in the intestine may be due, in part, to the decrement in the circulating level of 1,25-(OH)2D and a reduction of intestinal 1,25-(OH)2D3 receptor occupancy status.
我们证实了之前的观察结果,即与年轻(6个月大)大鼠相比,老年(24个月大)大鼠的十二指肠钙吸收和血清1,25 - 二羟基维生素D(1,25-(OH)₂D)水平同时下降。众所周知,1,25 - 二羟基维生素D₃(1,25-(OH)₂D₃)在与特定受体分子结合后发挥其作用。在本文中,我们比较了老年和年轻动物大鼠十二指肠1,25-(OH)₂D₃受体的某些特性。将受体制剂与[³H]1,25-(OH)₂D₃一起孵育,以定量未占据和总受体位点的数量,结果显示老年大鼠中总受体位点和未占据受体位点分别减少了22%和16%。老年大鼠十二指肠中内源性占据位点减少了43%,因此受体占据百分比也下降。年龄并不影响1,25-(OH)₂D₃从受体上的解离常数(KD);在蔗糖密度离心中氚化的1,25-(OH)₂D₃ - 受体复合物的沉降系数(3.3 S);或其对DNA的亲和力。这些数据与以下假设一致,即肠道中与年龄相关的钙吸收下降可能部分归因于1,25-(OH)₂D循环水平的降低以及肠道1,25-(OH)₂D₃受体占据状态的降低。