Identification of [hydroxyproline<sup>3</sup>]‐lysyl‐bradykinin released from human kininogens by human urinary kallikrein

Maier, Martin; Reissert, Guenther; Jerabek, Ingrid; Lottspeich, F.; Binder, Bernd R.

doi:10.1016/0014-5793(88)80778-6

Cited by 19 publications

(6 citation statements)

References 19 publications

(3 reference statements)

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“…bradykinin (BK) and hydroxyprolyl 3-bradykinin (Arg-Pro-Hyp-Gly-Phe-Ser-Pro-Phe-Arg), (Hyp 3-BK), in human tumor ascites and concluded that they are generated from high molecular weight kininogen [7,8]. We and other workers have also identified Hyp3-BK from normal human plasma or urine [9][10][11][12]. Because of the large capacity of generation of kinins and the potent activity of these peptides, they may be important in various pathological conditions.…”

Section: Introductionmentioning

confidence: 92%

Degradation pathway of kinins in tumor ascites and inhibition by kininase inhibitors: Analysis by HPLC

1990

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We have recently found presence of a high concentration of a novel type of kinin, hydroxyprolyl3-bradykinin (Hyp3-BK) in human tumor ascites in addition to conventional bradykinin (BK). Because of their potential physiological activity, it is of interest to know how these bradykinins can be degraded in ascites. Degradation of two synthetic kinins, BK and Hyp3-BK, added to the ascitic fluid from patients with ovarian carcinoma and hepatoma, were analyzed by reversed phase HPLC. Both kinins were degraded into their desArg9-BK or -Hyp3-BK and desPhe8-Arg-9-BK or -Hyp3-BK products following incubation with the ascitic fluid. The rate of the degradation of BK and Hyp3-BK was the same. The formation of desArg9-BK was completely inhibited by kininase I inhibitor, while the formation of desPhe8-Arg9-BK was not completely inhibited by a kininase II inhibitor. The degradation of both kinins was inhibited completely by EDTA. The results indicate the presence of other metalloprotease(s) which cleaves kinins in the ascitic fluid, in addition to kininase I and kininase II. The carboxypeptidase A and carboxypeptidase B inhibitor, benzyl malic acid, failed to block degradation of both kinins. A rapid cleave of Phe-Arg into Phe and Arg was also found in the ascitic fluid. Thus, the major degradation products of kinins in the ascitic fluid were demonstrated to be either desArg9-BK or Hyp3-BK, desPhe8-Arg9-BK or -Hyp3-BK, phenylalanine and arginine. Lysyl-BK and lysylhydroxyprolyl3-BK were rapidly converted into BK and hydroxyprolyl3-BK by the ascitic fluid.

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Section: Introductionmentioning

confidence: 92%

Degradation pathway of kinins in tumor ascites and inhibition by kininase inhibitors: Analysis by HPLC

1990

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“…Astonishingly enough, hydroxyla tion was found to vary widely between human H-and Lkininogen, respectively. Maier et al reported that Hyp3-Lysbradykinin represented 47% (range 30 to 59% , n = 4) of the total kinin peptides released from purified H-kininogen, whereas it was only 6% (from pool plasma) in the case of L-kininogen (19). The reason for this unexpected "differential" hydroxylation is unknown at the moment.…”

Section: Hydroxylation Of Kininogens and Kininsmentioning

confidence: 99%

“…Now these seem ingly contradictory observations have been reconciled. Four research groups including Scicli's team independently demon strate that Ala was incorrectly assigned to position 3 (18)(19)(20)(21)(22). Instead, 4-hydroxy-proline (Hyp) was identified in this position thus pointing to a post-translational modification of Pro in position 3.…”

Section: Hydroxylation Of Kininogens and Kininsmentioning

confidence: 99%

“…2). Not only were Hyp3-bradykinin and Hyp3-lysyl-bradykinin found in human urine and ascites (17, 18, 22) but they were also releasable from intact kininogens by kallikreins (19)(20)(21). This strongly suggests that the precursor molecules (rather than the liberated peptides) are subject to hydroxylation.…”

Section: Hydroxylation Of Kininogens and Kininsmentioning

confidence: 99%

“…Hydroxylation is thought to contribute to the conformational stability of these proteins, however, no evidence is available that would substanti ate such a hypothesis for kinin(ogen)s. One might reason that hydroxylation could alter kinin(ogen) function. Comparison of the biologic activity of kinins and hydroxylated derivatives thereof revealed no significant differences in the rat uterus assay (19) or in the dog hind limb test (17). Likewise, kinin release from the kininogens is virtually unaffected by hydroxylation as long as kallikrein from the same species is used (17).…”

Section: Hydroxylation Of Kininogens and Kininsmentioning

confidence: 99%

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Kininogens, Kinins and Kinships

Müller‐Esterl

1989

Thromb Haemost

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This article reviews most recent developments in the field of the multifunctional kininogens which are involved in major physiologic systems such as the blood coagulation cascade, the inflammatory reaction, the inhibitor defense mechanism, and the acute phase response. Particular attention is given to the interac tion of kininogens with endothelial cells and platelets, the post translational modification of kinin(ogen)s by proline hydroxylase, and the placing of kininogens among structurally and functionally related plasma proteins. Classic and Alternative Functions of Kininogens Mammalian blood coagulation is a well-orchestrated process of cellular and molecular events destined to the rapid occlusion of leaky blood vessels by thrombus formation (1). A large number of proteins are involved in the cascades that initiate and propagate blood coagulation, and among them are high-molecular-weight kininogen (H-kininogen)1 * * * and prekallikrein (PK). In concert with Hageman factor and factor X I they trigger the intrinsic blood coagulation cascade via the contact activation pathway (2). By contrast, the other type of kininogen present in human plasma, i.e. low-molecular-weight kininogen (L-kininogen) is devoid of any procoagulant activity. Apart from the role as a cofactor of the endogenous pathway, the kininogens function as the large precur sor molecules to small vasoactive peptides, the kinins. Typically, kinins are released from the single-chain kininogens of Mr 68,000 (L-kininogen) or 110,000 (H-kininogen) via limited proteolysis with specific kininogenases, e.g. the kallikreins. The kinins exert their effects via specific receptors exposed on their target cells and mediate vasodilatation, increase of vascular permeability, con traction of smooth muscles, and provocation of pain (3). Only recently, two novel functions of the kininogens seemingly unrelated to kinin release or contact phase binding were dis closed: first, their role as potent inhibitors of cysteine proteinases, and second, their specific involvement in the acute phase response of the rat (reviewed in refs. 4 and 5). This latter function is mediated by a third type of kininogen, T-kinirtogen (also named "major acute phase protein"), which has been found so far exclu sively in the rat. Hence, the kininogens are extremely versatile proteins which serve a plethora of distinct biologic roles, and their functional diversity is reflected by a complex multidomain struc ture (4). This article reviews some recent developments in the field of kininogens and kinins, thereby focusing on the cellular interactions of kininogens, the modification of the kinin(ogen)s by proline hydroxylation, and the evolutionary relationships among kininogens and other known plasma proteins.

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Kinins

Oliveira

Souza

Bäder

et al. 2008

Cardiovascular Hormone Systems

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Identification of [hydroxyproline³]‐lysyl‐bradykinin released from human kininogens by human urinary kallikrein

Cited by 19 publications

References 19 publications

Degradation pathway of kinins in tumor ascites and inhibition by kininase inhibitors: Analysis by HPLC

Degradation pathway of kinins in tumor ascites and inhibition by kininase inhibitors: Analysis by HPLC

Kininogens, Kinins and Kinships

Kinins

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Identification of [hydroxyproline3]‐lysyl‐bradykinin released from human kininogens by human urinary kallikrein

Cited by 19 publications

References 19 publications

Degradation pathway of kinins in tumor ascites and inhibition by kininase inhibitors: Analysis by HPLC

Degradation pathway of kinins in tumor ascites and inhibition by kininase inhibitors: Analysis by HPLC

Kininogens, Kinins and Kinships

Kinins

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Identification of [hydroxyproline³]‐lysyl‐bradykinin released from human kininogens by human urinary kallikrein