Shew R L, Robinson M F, Olansky L, Yee J A
Department of Anatomical Sciences, Oklahoma University Health Sciences Center, Oklahoma City.
Pharmacology. 1989;39(6):390-6. doi: 10.1159/000138628.
Synthetic bovine parathyroid hormone containing the 1-34 NH2-terminal amino acids [bPTH-(1-34)] inhibits uterine contraction stimulated by a variety of agonists. Previously, we reported that the parathyroid hormone analogue [Nle8, Nle18, Tyr34]bPTH-(3-34)amide [NTA-(3-34)] antagonized this effect of bPTH-(1-34) while the analogue [Tyr34]bPTH-(7-34)amide [bPTH-(7-34)] used in this study stimulated uterine contraction. However, contrary to this previous report, bPTH-(7-34) in the present study failed to initiate a contractile response and instead resulted in an inhibitory response to the bPTH-(1-34) effect on uterine contraction in a dose-related manner. The inhibitory response of bPTH-(7-34) was further confirmed by demonstrating that this preparation of bPTH-(7-34) was capable of blocking bPTH-(1-34)-stimulated adenylate cyclase activity on particulate fractions of osteoblast-like cells from neonatal mouse calvarial. These results are consistent with those in the literature for the antagonistic effect of the 7-34 PTH fragment.
含有1 - 34个N端氨基酸的合成牛甲状旁腺激素[bPTH-(1 - 34)]可抑制多种激动剂刺激引起的子宫收缩。此前,我们报道甲状旁腺激素类似物[Nle8, Nle18, Tyr34]bPTH-(3 - 34)酰胺[NTA-(3 - 34)]可拮抗bPTH-(1 - 34)的这种作用,而本研究中使用的类似物[Tyr34]bPTH-(7 - 34)酰胺[bPTH-(7 - 34)]可刺激子宫收缩。然而,与之前的报道相反,本研究中的bPTH-(7 - 34)未能引发收缩反应,反而以剂量相关的方式对bPTH-(1 - 34)对子宫收缩的作用产生抑制反应。通过证明这种bPTH-(7 - 34)制剂能够阻断bPTH-(1 - 34)刺激新生小鼠颅骨成骨样细胞微粒体部分的腺苷酸环化酶活性,进一步证实了bPTH-(7 - 34)的抑制反应。这些结果与文献中关于7 - 34 PTH片段拮抗作用的结果一致。