Metabolism of radioiodinated bovine parathyroid hormone in the rat.
Metabolism of radioiodinated bovine parathyroid hormone in the rat.
复制标题
大鼠体内放射性碘标记的牛甲状旁腺激素的代谢。
作者：
G. V. Segre;Pierre D’Amour;John T. Potts
通过凝胶过滤和碘化片段的序列分析，研究了大鼠体内牛 125I 标记的甲状旁腺激素的代谢。激素代谢动力学分析表明，碘化完整激素具有多指数消失曲线，初始成分快速（3 分钟），第二成分较慢（48 分钟）。注射完整激素后的前 12 分钟内，碘化片段迅速增加，随后从循环中消失，t1/2 不超过 48 分钟。静脉注射牛 125I 标记的甲状旁腺激素后在不同时间间隔收集的血浆样品在 Bio-gel P-100 上进行凝胶过滤。观察到四个放射性峰。第一个和第二个峰分别在柱的空隙体积处和完整激素的位置处洗脱。第三个峰由碘化片段组成，最后一个峰在柱的盐体积处洗脱。对第三个峰中碘化片段的序列分析表明，它是异质的，包含几种不同但密切相关的多肽。注射后 48 分钟之前，最丰富的片段是氨基末端氨基酸为残基 34 的片段。下一个最常见片段的氨基末端残基是位置 37 的氨基酸。没有看到比残基 34 更接近氨基末端的裂解片段。这些研究的结果与之前在狗身上获得的结果几乎相同。在大鼠和狗的激素蛋白水解位点和激素代谢动力学中发现的相似性，加上不太直接的证据表明类似的裂解也存在于人和牛中，这与甲状旁腺激素的蛋白水解是外周组织是特异性的（至少在哺乳动物物种中）是一致的，并且可能是控制甲状旁腺激素的可用性的关键步骤。 生物活性激素。
Metabolism of bovine 125I-labeled parathyroid hormone was studied in the rat by gel filtration and by sequence analysis of the iodinated fragments. Analysis of the kinetics of hormone metabolism shows that iodinated intact hormone has a multiexponential disappearance curve with a rapid (3 min) initial and a slower (48 min) second component. Iodinated fragments, which rapidly increase during the first 12 min after injection of the intact hormone, subsequently disappear from the circulation with a t1/2 of no greater than 48 min. Plasma samples collected at various time-intervals after intravenous injection of bovine 125I-labeled parathyroid hormone were gel filtered on Bio-gel P-100. Four radioactive peaks were seen. The first and second peaks eluted, respectively, at the void volume of the column and at the position of intact hormone. The third peak consisted of iodinated fragments, and the last peak eluted at the salt volume of the column. Sequence analysis of the iodinated fragments in the third peak showed that it was heterogeneous, containing several different, but closely related, polypeptides. Before 48 min after injection, the most-abundant fragment is one whose amino-terminal amino acid is residue 34. The amino-terminal residue of the next most-common fragment is the amino acid at position 37. No fragments representing cleavages closer to the amino-terminus than residue 34 were seen. The results of these studies are virtually identical with those previously obtained in the dog. The similarities found in the sites of hormone proteolysis and in the kinetics of hormone metabolism in the rat and dog, coupled with the less direct evidence indicating that similar cleavages are also present in man and bovine, are consistent with the view that proteolysis of parathyroid hormone is peripheral tissues is specific, at least in mammalian species, and may be a critical step in controlling the availability of biologically active hormone.