Ufkes J G, Aarsen P N, van der Meer C
Eur J Pharmacol. 1977 Jul 15;44(2):89-97. doi: 10.1016/0014-2999(77)90094-2.
Bradykinin-induced contractions in the guinea-pig ileum were potentiated by the peptides A-VI-5 (Val-Glu-Ser-Ser-Lys) and BPP5a (Pyr-Lys-Trp-Ala-Pro), while the contractions induced by other agonists were not affected. Neither peptide added alone caused any response. Previous addition of the peptides shortened the latent period following the addition of bradykinin to a value corresponding to the contraction height with an equivalent dose of bradykinin added alone. Bradykinin in contact with a piece of ileum was inactivated at a relatively slow rate. This inactivation was not inhibited by either A-VI-5 or BPP5a in doses causing potentiation. Suppression of the cholinergic activity by cooling, atropine, morphine or tetrodotoxin did not influence the potentiating activity. Addition of the peptides at the moment a submaximal contraction due to bradykinin had been fully established, increased the contraction height within seconds. The two peptides caused a parallel shift to the left of the dose-effect curve of bradykinin, whereas the maximum bradykinin effect remained unchanged. It is concluded that sensitization of bradykinin receptors due to an increased affinity of the receptor for bradykinin is the hypothesis which best fits the experimental findings.
肽A-VI-5（缬氨酸-谷氨酸-丝氨酸-丝氨酸-赖氨酸）和BPP5a（焦谷氨酸-赖氨酸-色氨酸-丙氨酸-脯氨酸）可增强豚鼠回肠中缓激肽诱导的收缩，而其他激动剂诱导的收缩则不受影响。单独添加这两种肽均未引起任何反应。预先添加这些肽可将添加缓激肽后的潜伏期缩短至与单独添加等量缓激肽时的收缩高度相对应的值。与一段回肠接触的缓激肽以相对较慢的速率失活。在引起增强作用的剂量下，A-VI-5或BPP5a均未抑制这种失活。通过冷却、阿托品、吗啡或河豚毒素抑制胆碱能活性并不影响增强活性。在由缓激肽引起的次最大收缩完全建立时添加这些肽，可在数秒内增加收缩高度。这两种肽使缓激肽的剂量-效应曲线向左平行移动，而缓激肽的最大效应保持不变。得出的结论是，由于受体对缓激肽的亲和力增加而导致缓激肽受体致敏是最符合实验结果的假说。
