kallidin and amastatin

kallidin has been researched along with amastatin* in 3 studies

Other Studies

3 other study(ies) available for kallidin and amastatin

ArticleYear
Functional evidence of des-Arg10-kallidin enzymatic inactivating pathway in isolated human umbilical vein.
    Naunyn-Schmiedeberg's archives of pharmacology, 2007, Volume: 375, Issue:3

    It has been known for many years that plasma and tissues contain a variety of enzymes capable of metabolizing kinins. The aim of the present study was to evaluate, by means of functional studies in a capacitance vessel such as the human umbilical vein (HUV), the possible role played by the metallopeptidases angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP), and aminopeptidase M (APM) as an inactivating pathway of the B(1) receptor endogenous agonist des-Arg(10)-kallidin (DAKD). In HUV rings with and without endothelium, concentration-response curves (CRCs) to DAKD were determined after a 300-min incubation period, and enzymatic inhibitors were added to the organ baths 30 min before construction of the CRC. Presence of endothelial layer was confirmed by histological studies. There was a significant leftward shift observed in control HUV rings devoid of endothelium compared with intact tissues. Exposure to 1 microM captopril (ACE inhibitor) potentiated DAKD-elicited vasoconstrictor responses in HUV rings with endothelium while no such effect was observed in tissues devoid of endothelium. Application of 10 microM amastatin (APM inhibitor) induced a leftward shift of DAKD-elicited contractile responses in HUV with and without endothelium. On the other hand, 10 microM phosphoramidon (NEP inhibitor) showed no potentiating effect in HUV rings either with or without endothelium. However, under concurrent inhibition of ACE, NEP and APM, there was a higher potentiation of DAKD-elicited contractile responses compared with the effect observed with combined inhibition of ACE and APM. Moreover, when we evaluated contractile responses induced by Sar(0)-D-Phe(8)-des-Arg(9)-BK (a metabolically protected B(1) receptor agonist), no potentiating effect was observed under triple enzymatic inhibition. In conclusion, in the present study for the first time, we demonstrated in a capacitance vessel, HUV, that metallopeptidases ACE, NEP and APM represent a relevant functional inactivation pathway of DAKD.

    Topics: Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Captopril; CD13 Antigens; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Female; Glycopeptides; Humans; In Vitro Techniques; Kallidin; Metalloproteases; Neprilysin; Peptides; Protease Inhibitors; Receptor, Bradykinin B1; Umbilical Veins; Vasoconstriction

2007
Identification of kallidin degrading enzymes in the isolated perfused rat heart.
    Japanese journal of pharmacology, 1999, Volume: 79, Issue:1

    Kallidin (KD) is an important vasoactive kinin whose physiological effects are strongly dependent on its degradation through local kininases. In the present study, we examined the spectrum of these enzymes and their contribution to KD degradation in isolated perfused rat hearts. By inhibiting angiotensin-converting enzyme (ACE), aminopeptidase M (APM) and neutral endopeptidase (NEP) with ramiprilat (0.25 microM), amastatin (40 microM) and phosphoramidon (1 microM), respectively, relative kininase activities were obtained. APM (44%) and ACE (35%) are the main KD degrading enzymes in rat heart; NEP (7%) plays a minor role. A participation of carboxypeptidase N (CPN) could not be found.

    Topics: Aminopeptidases; Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Bacterial Agents; Glycopeptides; In Vitro Techniques; Kallidin; Male; Myocardium; Neprilysin; Peptide Hydrolases; Peptides; Peptidyl-Dipeptidase A; Perfusion; Protease Inhibitors; Ramipril; Rats; Rats, Wistar

1999
Kallidin- and bradykinin-degrading pathways in human heart: degradation of kallidin by aminopeptidase M-like activity and bradykinin by neutral endopeptidase.
    Circulation, 1999, Apr-20, Volume: 99, Issue:15

    Since kinins kallidin (KD) and bradykinin (BK) appear to have cardioprotective effects ranging from improved hemodynamics to antiproliferative effects, inhibition of kinin-degrading enzymes should potentiate such effects. Indeed, it is believed that this mechanism is partly responsible for the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors. In the heart, enzymes other than ACE may contribute to local degradation of kinins. The purpose of this study was to investigate which enzymes are responsible for the degradation of KD and BK in human heart tissue.. Cardiac membranes were prepared from the left ventricles of normal (n=5) and failing (n=10) hearts. The patients had end-stage congestive heart failure as the result of coronary heart disease or idiopathic dilated cardiomyopathy. Heart tissue was incubated with KD or BK in the presence or absence of enzyme inhibitors. We found no difference in the enzymes responsible for kinin metabolism or their activities between normal and failing hearts. Thus KD was mostly converted into BK by the aminopeptidase M-like activity. When BK was used as substrate, it was converted into an inactive metabolite BK-(1-7) mostly (80% to 90%) by the neutral endopeptidase (NEP) activity, with ACE unexpectedly playing only a minor role. The low enzymatic activity of ACE in the cardiac membranes, compared with that of NEP, was not due to chronic ACE inhibitor therapy, because the cardiac ACE activities of patients, whether receiving ACE inhibitors or not, and of normal subjects were all equal.. The present in vitro study shows that in human cardiac membranes, the most critical step in kinin metabolism, that is, inactivation of BK, appears to be mediated mostly by NEP. This observation suggests a role for NEP in the local control of BK concentration in heart tissue. Thus inhibition of cardiac NEP activity could be cardioprotective by elevating the local concentration of BK in the heart.

    Topics: Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Bradykinin; Captopril; CD13 Antigens; Dipeptides; Female; Glycopeptides; Heart Failure; Humans; Kallidin; Leucine; Male; Membrane Proteins; Middle Aged; Myocardium; Neprilysin; Peptides; Peptidyl-Dipeptidase A; Protease Inhibitors; Substrate Specificity

1999