Analysis of the antagonistic actions of HOE 140 and other novel bradykinin analogues on the guinea-pig ileum.
Analysis of the antagonistic actions of HOE 140 and other novel bradykinin analogues on the guinea-pig ileum.
复制标题
HOE 140 和其他新型缓激肽类似物对豚鼠回肠的拮抗作用分析。
DOI：
10.1016/0014-2999(92)90397-m
复制
发表时间：
1992
影响因子：
5
通讯作者：
F. Lembeck
中科院分区：
文献类型：
--
作者：
T. Griesbacher;F. Lembeck
将3种新型缓激素（BK）拮抗剂D-Arg-[Hyp3， Thi5, D-Tic7, Oic8]BK （ho140，化合物I）、D-Arg-[Hyp3, D-Tic7, Oic8]BK（化合物II）和[Arg(Tos)1, Hyp3, Thi5, D-Tic7, Oic8]BK（化合物III）与传统拮抗剂D-Arg-[Hyp2， Thi5,8, D-Phe7]BK（化合物IV）在豚鼠回肠上的拮抗作用进行了比较。新化合物诱导累积浓度-反应曲线向右偏移，并伴有最大效应（Emax）的逐渐降低，但斜率没有显著降低，而化合物IV没有观察到Emax的降低。P物质对豚鼠回肠和加压素对大鼠子宫的作用完全不受影响。结果表明，新型BK类似物在豚鼠回肠中具有竞争性和非竞争性抑制作用，但抑制是可逆的和特异性的，因此它们是双重拮抗剂。
The type of antagonism exhibited by three novel bradykinin (BK) antagonists, D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]BK (HOE 140, compound I), D-Arg-[Hyp3, D-Tic7, Oic8]BK (compound II) and [Arg(Tos)1, Hyp3, Thi5, D-Tic7, Oic8]BK (compound III), was compared with that of a conventional antagonist, D-Arg-[Hyp2, Thi5,8, D-Phe7]BK (compound IV), on the guinea-pig ileum. The novel compounds induced rightward displacements of cumulative concentration-response curves to BK, accompanied by a progressive reduction of the maximum effect (Emax) without a significant decrease in the slope, whereas no reduction of Emaxwas observed with compound IV. Actions of substance P on the guinea-pig ileum and of vasopressin on the rat uterus remained completely unaffected. It is concluded that as the novel BK analogues show competitive as well as non-competitive inhibition in the guinea-pig ileum, but the inhibition is reversible and specific, they are dual antagonists.