No abstract

No abstract

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 characterization of two new peptides generated by tryptic hydrolysis of casein. No homology was found with other known vasoactive or vasopotentiating peptides, especially by the lack of Ile-Pro-Pro motif. The peptides EMPFPK and YPVEPFTE, corresponding to the gamma casein sequence (108-113 and 114-121, respectively), displayed a selective potentiating activity on isolated guinea pig ileum for bradykinin. Besides, the octapeptide YPVEPFTE showed an in vitro competitive inhibitor effect on angiotensin-converting enzyme and thimet oligopeptidase and presented an opiate-like activity, increasing two times the latence time in the hot-plate assay. The results suggest that the isolated bioactive peptides act on conversion and/or inactivation of endogenous peptides by enzymes such as angiotensin-converting enzyme and thimet oligopeptidase by modifying several systemic responses such as blood-pressure regulation and in pain response.

No abstract

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.