Lebrun I, Lebrun F L, Henriques O B, Carmona A K, Juliano L, Camargo A C
Biochemistry Laboratory, Butantan Institute, São Paulo, Brazil.
Can J Physiol Pharmacol. 1995 Jan;73(1):85-91. doi: 10.1139/y95-012.
Peptides that display bradykinin-potentiating activity have been obtained from a number of distinct sources, such as snake venoms, fibrinogen, and casein. This paper describes the isolation and sequencing of a novel bradykinin-potentiating peptide, generated by tryptic hydrolysis of the gamma-casein chain. No homology was found to other known vasoactive or vasopotentiating peptides. The octapeptide Tyr-Pro-Val-Gln-Pro-Phe-Thr-Glu, corresponding to the gamma-casein(114-121) sequence, was isolated from the tryptic hydrolysis of gamma-casein and also synthesized by solid-phase peptide synthesis. Both natural and synthetic peptides had the same retention time in HPLC and displayed a selective potentiating activity on isolated guinea-pig ileum for bradykinin and Lys-bradykinin but were not able to potentiate the effects of Met-Lys-bradykinin, Ile-Ser-bradykinin, angiotensin II, acetylcholine, or histamine. Intravenous injections of bradykinin and of bradykinin-potentiating octapeptide produced a persistent hypotension in conscious rats, a pattern that was not obtained when the octapeptide was replaced by captopril. This bradykinin-potentiating octapeptide is a strong competitive inhibitor of endo-oligopeptidase A (EC 3.4.24.15, formerly EC 3.4.22.19), but it has low inhibitory potency towards angiotensin-converting enzyme (EC 3.4.15.1). Thus, our results suggest that other peptidases in addition to angiotensin-converting enzyme, such as endo-oligopeptidase A, may contribute to the reduction of the effective concentration of bradykinin in the circulation.
已从多种不同来源获得具有缓激肽增强活性的肽，如蛇毒、纤维蛋白原和酪蛋白。本文描述了一种新型缓激肽增强肽的分离和测序，该肽由γ-酪蛋白链的胰蛋白酶水解产生。未发现与其他已知血管活性或血管增强肽有同源性。从γ-酪蛋白的胰蛋白酶水解物中分离出对应于γ-酪蛋白(114 - 121)序列的八肽Tyr-Pro-Val-Gln-Pro-Phe-Thr-Glu，并通过固相肽合成法合成。天然和合成肽在高效液相色谱中的保留时间相同，对分离的豚鼠回肠中的缓激肽和赖氨酸缓激肽具有选择性增强活性，但不能增强甲硫氨酸-赖氨酸缓激肽、异亮氨酸-丝氨酸缓激肽、血管紧张素II、乙酰胆碱或组胺的作用。静脉注射缓激肽和缓激肽增强八肽可使清醒大鼠持续低血压，当八肽被卡托普利替代时则未出现这种情况。这种缓激肽增强八肽是内肽酶A（EC 3.4.24.15，原EC 3.4.22.19）的强竞争性抑制剂，但对血管紧张素转换酶（EC 3.4.15.1）的抑制效力较低。因此，我们的结果表明，除血管紧张素转换酶外，其他肽酶，如内肽酶A，可能有助于降低循环中缓激肽的有效浓度。
