Vavrek R J, Stewart J M
Peptides. 1985 Mar-Apr;6(2):161-4. doi: 10.1016/0196-9781(85)90033-6.
The first sequence-related competitive inhibitors of the classic kinin in vitro (rat uterus guinea pig ileum) and in vivo (rat blood pressure) assays have been developed. Replacement of the proline residue at position 7 of bradykinin (BK) with a D-phenylalanine residue is the key modification which converts BK agonists into antagonists. [D-Phe7]-BK exhibits moderate (pA2 = 5.0) inhibition of BK activity on the guinea pig ileum but possesses weak BK-like myotropic activity on the isolated rat uterus and 2-4% of BK depressor potency in the rat blood pressure assay. The additional replacement of the phenylalanine residues at positions 5 and 8 of [D-Phe7]-BK with the isosteric beta-(2-thienyl)-alanine residue produces a potent antagonist of BK activity on the uterus (pA2 = 6.4), ileum (pA2 = 6.3), and in the rat blood pressure assay. The antagonism of BK action on smooth muscle is specific for kinins (BK, kallidin, Met-Lys-BK), but neither inhibitor antagonizes the smooth muscle activity of angiotensin or substance P. Inhibition is competitive and fully reversible.
已开发出经典激肽在体外（大鼠子宫、豚鼠回肠）和体内（大鼠血压）试验中的首批序列相关竞争性抑制剂。用D-苯丙氨酸残基取代缓激肽（BK）第7位的脯氨酸残基是将BK激动剂转化为拮抗剂的关键修饰。[D-Phe7]-BK对豚鼠回肠的BK活性表现出中等程度（pA2 = 5.0）的抑制作用，但对离体大鼠子宫具有较弱的BK样肌otropic活性，在大鼠血压试验中具有BK降压效力的2 - 4%。用等排体β-(2-噻吩基)-丙氨酸残基额外取代[D-Phe7]-BK第5位和第8位的苯丙氨酸残基，可产生一种对子宫（pA2 = 6.4）、回肠（pA2 = 6.3）以及大鼠血压试验中BK活性的强效拮抗剂。BK对平滑肌作用的拮抗作用对激肽（BK、胰激肽、Met-Lys-BK）具有特异性，但两种抑制剂均不拮抗血管紧张素或P物质的平滑肌活性。抑制作用具有竞争性且完全可逆。
