Atke A, Vilhardt H, Melin P
Department of Medical Physiology C, Panum Institute, University of Copenhagen, Denmark.
J Endocrinol. 1988 Aug;118(2):187-92. doi: 10.1677/joe.0.1180187.
Purified myometrial plasma membrane fractions were prepared from rats treated with oestradiol to induce oestrus. The binding affinities of 11 antagonistic oxytocin analogues to the oxytocin receptor of the plasma membranes were measured. Furthermore, lipophilicity of the peptides was assessed by reversed-phase high pressure liquid chromatography. No significant correlation was found between lipophilicity of the analogues and values for antagonistic potencies or binding affinities. Also, receptor-binding affinity did not correlate with in-vitro antagonistic activity whereas a significant correlation was obtained between binding affinities and in-vivo antagonistic potency for analogues void of partial agonist properties. It is concluded that neither receptor affinity nor lipophilicity in the analogues can predict the potency of the antagonists in vitro. However, receptor affinity was found to be a relatively good predictor of the in-vivo potency, while the usefulness of measuring antagonistic potency in vitro is questioned.
从用雌二醇处理以诱导发情的大鼠中制备纯化的子宫肌层质膜组分。测定了11种拮抗催产素类似物与质膜催产素受体的结合亲和力。此外，通过反相高压液相色谱法评估肽的亲脂性。在类似物的亲脂性与拮抗效力或结合亲和力值之间未发现显著相关性。同样，受体结合亲和力与体外拮抗活性无关，而对于没有部分激动剂特性的类似物，结合亲和力与体内拮抗效力之间存在显著相关性。得出的结论是，类似物中的受体亲和力和亲脂性均不能预测拮抗剂的体外效力。然而，发现受体亲和力是体内效力的相对良好预测指标，而体外测定拮抗效力的实用性受到质疑。
