Evaluation of the biological properties of parathyroid hormone and analogues in a vascularly isolated parotid gland-based assay.
Evaluation of the biological properties of parathyroid hormone and analogues in a vascularly isolated parotid gland-based assay.
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DOI：
10.1677/joe.0.1020375
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发表时间：
1984-09
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影响因子：
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通讯作者：
R. D. Wright;J. Blair-west;J. Nelson;G. Tregear;M. Rosenblatt
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文献类型：
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作者：
R. D. Wright;J. Blair-west;J. Nelson;G. Tregear;M. Rosenblatt
将牛甲状旁腺激素（bPTH）制剂输注到麻醉绵羊的血管隔离腮腺的动脉血供中，可增加唾液磷酸盐浓度和腺体血流速度，并具有快速起效和抵消作用。这些响应已被用作PTH和PTH类似物的生物测定，并用于评估体外抑制性类似物[Nle-8，Nle-18，Tyr-34]bPTH-（3-34）酰胺的性质。在唾液磷酸盐和血流测定中，10（-9）至10（-8）mol/l的[Nle-8，Nle-18，Tyr-34]bPTH-（1 - 34）酰胺的效力是bPTH（1-34）的4至5倍。人PTH（1-34）的效力并不显著高于bPTH（1-34）。[Nle-8，Nle-18，Tyr-34]bPTH-（3-34）酰胺类似物在3 × 10 ~（-7）mol/l时有极轻微的激动活性，当类似物与PTH的比例为100：1时，它完全抑制bPTH（1-34）对磷酸盐分泌和腺血流量的作用。在10：1时有部分抑制作用，在1：1时无明显抑制作用。这些结果不同于以前的体外结果，并表明该制剂可能是有价值的评估的激动剂和拮抗剂类似物的PTH。绵羊的血管分离腮腺允许在对照-测试-对照序列中重复随机测试类似物，结果表明在具有两个响应参数的快速反应性体内系统中对PTH具有高灵敏度。
Infusion of bovine parathyroid hormone (bPTH) preparations into the arterial blood supply of the vascularly isolated parotid gland in anaesthetized sheep increases salivary phosphate concentration and gland blood flow rate with rapid onset and offset of action. These responses have been used as a bioassay for PTH and PTH analogues and for assessing the properties of an in-vitro inhibitory analogue [Nle-8, Nle-18, Tyr-34]bPTH-(3-34)amide. [Nle-8, Nle-18, Tyr-34]bPTH-(1-34)amide at 10(-9) to 10(-8) mol/l was four to five times more potent than bPTH(1-34) on both salivary phosphate and blood flow assays. Human PTH(1-34) was not significantly more potent than bPTH(1-34). The [Nle-8, Nle-18, Tyr-34]bPTH-(3-34)amide analogue had very slight agonist activity at 3 X 10(-7) mol/l and at a 100:1 ratio of analogue to PTH it completely inhibited the action of bPTH(1-34) on phosphate secretion and gland blood flow. It caused partial inhibition at 10:1 and had no evident effect at 1:1. These results differ from previous in-vitro results and indicate that the preparation may be valuable for evaluation of agonist and antagonist analogues of PTH. The vascularly isolated parotid gland of the sheep permits repeated random testing of analogues in a control-test-control sequence and the results indicate high sensitivity to PTH in a rapidly reactive in-vivo system with two responding parameters.