Gao X, Stewart J M, Vavrek R J, Greenbaum L M
Department of Pharmacology, School of Graduate Studies, Medical College of Georgia, Augusta 30912.
Biochem Pharmacol. 1993 Nov 2;46(9):1607-12. doi: 10.1016/0006-2952(93)90330-y.
T-Kinin (Ile-Ser-bradykinin) is unique to the rat. This study characterizes the receptors involved in T-kinin activity on both the intact isolated rat uterus and membrane receptor preparations of the rat uterus. The results show that T-kinin acts through kinin B2 receptors in the rat uterus as demonstrated by B2 receptor-antagonist inhibition. While the potency of T-kinin on rat uterus contraction was similar to that of bradykinin, binding studies showed that the affinity of T-kinin to the receptor was 10-fold lower than that of bradykinin. On the other hand, the D isomer of T-kinin, D-Ile-Ser-bradykinin, had an affinity for the receptor greater than that of T-kinin and was more potent in causing contraction. Comparing this finding with our previously published report that D-Ile-Ser-bradykinin is not active on the kinin receptor for vascular permeability indicates that the kinin receptors in the rat uterus are not the same as those previously reported in the smooth muscle of the vasculature, i.e. there exists subclasses of kinin B2 receptors. The data from binding studies on a variety of T-kinin analogues show that the substitution of hydroxyproline (Hyp) for Pro5, together with the D-configuration at Ile1 and/or Ser2 may be useful for the development of selective T-kinin antagonists. Studies involving pretreatment of the tissue with indomethacin demonstrated that prostaglandin release was more of a component of T-kinin's activity on the rat uterus than that of bradykinin.
T-激肽（异亮氨酸-丝氨酸-缓激肽）是大鼠特有的。本研究对完整离体大鼠子宫和大鼠子宫膜受体制剂上参与T-激肽活性的受体进行了表征。结果表明，如B2受体拮抗剂抑制所示，T-激肽通过大鼠子宫中的激肽B2受体发挥作用。虽然T-激肽对大鼠子宫收缩的效力与缓激肽相似，但结合研究表明，T-激肽与受体的亲和力比缓激肽低10倍。另一方面，T-激肽的D异构体，D-异亮氨酸-丝氨酸-缓激肽，对受体的亲和力大于T-激肽，并且在引起收缩方面更有效。将这一发现与我们之前发表的报告（D-异亮氨酸-丝氨酸-缓激肽对血管通透性的激肽受体无活性）进行比较表明，大鼠子宫中的激肽受体与之前在血管平滑肌中报道的受体不同，即存在激肽B2受体亚类。对多种T-激肽类似物的结合研究数据表明，用羟脯氨酸（Hyp）取代Pro5，以及在Ile1和/或Ser2处的D构型，可能有助于开发选择性T-激肽拮抗剂。涉及用吲哚美辛预处理组织的研究表明，前列腺素释放比缓激肽更是T-激肽在大鼠子宫上活性的一个组成部分。
