Pang P K, Yang M C, Keutmann H T, Kenny A D
Endocrinology. 1983 Jan;112(1):284-9. doi: 10.1210/endo-112-1-284.
The present study was conducted to show that the hypercalcemic and the vascular relaxing activities of PTH are two separable properties. During the hypotensive action of the synthetic fragment bovine (b) PTH-(1-34), plasma calcium levels were not significantly changed. Mild oxidation with hydrogen peroxide abolished the hypotensive and hypercalcemic actions of bPTH-(1-84). However, the same treatment on bPTH-(1-34) abolished only the hypotensive and not the hypercalcemic action. Analysis of the amino acid composition revealed only the oxidation of the methionines to methionine sulfoxides. The other amino acids remained unchanged. In addition, the analog with methionines replaced by norleucine, [Nle8,Nle18,Tyr34]bPTH-(1-34), was active in all the vascular assays, and these activities were unaffected by hydrogen peroxide treatment of the molecule. Perhaps the methionine sulfoxides in the hydrogen peroxide-treated bPTH-(1-34) affected the changes of the molecule in such a manner that the part of the molecule for the vascular action but not that for the hypercalcemic action was no longer accessible to the receptors of the target organs. The hypotensive pentapeptide, bPTH-(24-28), was not active in the hypercalcemic assay. All these data are consistent with our hypothesis that the vascular relaxing and the hypercalcemic actions of PTH are two separate properties of the molecule.
本研究旨在表明甲状旁腺激素（PTH）的高钙血症作用和血管舒张作用是两种可分离的特性。在合成片段牛（b）PTH-（1-34）的降压作用过程中，血浆钙水平没有显著变化。用过氧化氢进行轻度氧化消除了bPTH-（1-84）的降压和高钙血症作用。然而，对bPTH-（1-34）进行相同处理仅消除了降压作用，而没有消除高钙血症作用。氨基酸组成分析显示只有甲硫氨酸氧化为甲硫氨酸亚砜。其他氨基酸保持不变。此外，甲硫氨酸被正亮氨酸取代的类似物[Nle8,Nle18,Tyr34]bPTH-（1-34）在所有血管检测中均有活性，并且这些活性不受分子过氧化氢处理的影响。也许过氧化氢处理的bPTH-（1-34）中的甲硫氨酸亚砜以这样一种方式影响分子的变化，即分子中负责血管作用的部分而非负责高钙血症作用的部分不再能够被靶器官的受体识别。降压五肽bPTH-（24-28）在高钙血症检测中没有活性。所有这些数据都与我们的假设一致，即PTH的血管舒张作用和高钙血症作用是该分子的两种独立特性。
