Rodrigues M S, Schaffel R, Assreuy J
Departamento de Farmacologia Basica e Clinica, Universidade Federal do Rio de Janeiro, Brazil.
Eur J Pharmacol. 1992 Jun 17;216(3):357-62. doi: 10.1016/0014-2999(92)90431-3.
The action of a kinin-potentiating peptide (KPP) obtained from tryptic digestion of human serum proteins was compared with that of bradykinin-potentiating peptide 9a (BPP9a; obtained from snake venom) and enalaprilat (a synthetic inhibitor of angiotensin-converting enzyme; ACE) as a means of understanding the mechanism of action of KPP on smooth muscle. KPP potentiated bradykinin-induced contractile effects in guinea-pig ileum and rat uterus, but not the bradykinin-induced relaxation of pre-contracted ileum, whereas BPP9a and enalaprilat potentiated both bradykinin effects. The receptor mediating both the contraction and the relaxation elicited by bradykinin in the ileum was found to be of the B2 type. KPP retained its potentiating effect in the presence of enalaprilat in the guinea-pig ileum and rat uterus, whereas the potentiation evoked by BPP9a was abolished. Enalaprilat inhibited the activity of purified ACE, whereas KPP was completely devoid of such an effect. The potentiating effect of KPP, but not that of BPP9a or enalaprilat, was blocked by compounds that inhibit phospholipase A2 and lipoxygenase activity but not by inhibitors of cyclo-oxygenase or phosphodiesterases. The results suggest that the potentiating effect of KPP (i) does not involve inhibition of ACE; (ii) is not due to an increased affinity of the receptor for bradykinin, and (iii) probably involves post-receptor events linked to phospholipase A2 and to the lipoxygenase pathway.
对从人血清蛋白胰蛋白酶消化产物中获得的激肽增强肽（KPP）的作用，与缓激肽增强肽9a（BPP9a；从蛇毒中获得）和依那普利拉（一种血管紧张素转换酶合成抑制剂；ACE）进行了比较，以此作为了解KPP对平滑肌作用机制的一种手段。KPP增强了缓激肽对豚鼠回肠和大鼠子宫的收缩作用，但对缓激肽诱导的预收缩回肠的舒张作用没有增强，而BPP9a和依那普利拉对缓激肽的两种作用均有增强。发现介导缓激肽在回肠中引起收缩和舒张的受体是B2型。在豚鼠回肠和大鼠子宫中，KPP在依那普利拉存在的情况下仍保留其增强作用，而BPP9a引起的增强作用则被消除。依那普利拉抑制纯化的ACE的活性，而KPP完全没有这种作用。KPP的增强作用，但不是BPP9a或依那普利拉的增强作用，被抑制磷脂酶A2和脂氧合酶活性的化合物所阻断，但不被环氧化酶或磷酸二酯酶抑制剂所阻断。结果表明，KPP的增强作用（i）不涉及ACE的抑制；（ii）不是由于受体对缓激肽的亲和力增加，并且（iii）可能涉及与磷脂酶A2和脂氧合酶途径相关的受体后事件。
