Bradykinin competitive antagonists for classical kinin systems.
Bradykinin competitive antagonists for classical kinin systems.
复制标题
经典激肽系统的缓激肽竞争性拮抗剂。
DOI：
10.1007/978-1-4684-5143-6_71
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发表时间：
1986
影响因子：
--
通讯作者：
Vavrek,RJ
中科院分区：
文献类型：
--
作者：
Stewart,JM;Vavrek,RJ
d -苯丙氨酸取代了缓激肽（BK）第7位的脯氨酸，将BK转化为一种特异性拮抗剂。非肽结构的额外修饰，特别是在5位和8位苯基丙氨酸的β-2-噻吩丙氨酸残基（Thi）的包含，增加了经典平滑肌（离体大鼠子宫和豚鼠回肠）和大鼠血压kinin测定中的拮抗剂效能。[thi5,8，DPhe7]-BK对大鼠子宫抑制的pa2值为6.5，对豚鼠回肠抑制的pa2值为6.3。在d - phe7取代拮抗剂的n端添加赖氨酸-赖氨酸或d -精氨酸-残基会降低子宫激动剂的活性，但不影响对回肠的抑制效力。添加d -脯氨酸残基取代d -精氨酸延伸拮抗剂3位脯氨酸产生特异性子宫抑制剂，对回肠无拮抗作用。d - phe7类似物不抑制平滑肌对p物质或血管紧张素ii的反应，并且对激肽反应的拮抗是竞争性的。
The substitution of D-phenylalanine for proline at position 7 of bradykinin (BK) converts BK into a specific antagonist. Additional modifications of the nonapeptide structure, especially the inclusion of β-2-thienylalanine residues (Thi) for phenylalanine at positions 5 and 8, increase antagonist potency in the classic smooth muscle (isolated rat uterus and guinea pig ileum) and rat blood pressure kinin assays. [ Thi5,8,DPhe7]-BK had a pA2value of 6.5 for inhibition of the BK response on rat uterus, and 6.3 on guinea pig ileum. Addition of Lys-Lys- or a D-Arg- residue to the N-terminal of D-Phe7-substituted antagonists decreases uterine agonist activity, but does not affect inhibitory potency on the ileum. Addition of a D-proline residue in place of proline in position 3 of D-Arg- extended antagonists produces specific uterine inhibitors which show no antagonism on the ileum. The D-Phe7-analogs did not inhibit smooth muscle responses to substance-P or angiotensin-II, and the antagonism of kinin responses was competitive.