Met-Lys-bradykinin-Ser-Ser, a peptide produced by the neutrophil from kininogen, is metabolically activated by angiotensin converting enzyme in vascular tissue
| Autor: | Johanne Bouthillier, Lajos Gera, François Marceau, Albert Adam, Caroline Roy, Marie-Thérèse Bawolak |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Enalaprilat Neutrophils High-molecular-weight kininogen Bradykinin Peptidyl-Dipeptidase A Pharmacology Muscle Smooth Vascular Umbilical vein 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Humans Amino Acid Sequence Receptor 030304 developmental biology 0303 health sciences Kininogen biology Kininogens Receptors Bradykinin Angiotensin-converting enzyme Kinin Endocrinology chemistry Mutation biology.protein Rabbits 030217 neurology & neurosurgery Muscle Contraction medicine.drug |
| Zdroj: | Pharmacological Research. 64:528-534 |
| ISSN: | 1043-6618 |
| DOI: | 10.1016/j.phrs.2011.08.001 |
| Popis: | Bradykinin (BK) is a vasoactive nonapeptide cleaved from circulating kininogens and that is degraded by angiotensin converting enzyme (ACE). It has been reported that the PR3 protease from human neutrophil releases an alternate peptide of 13 amino acids, Met-Lys-BK-Ser-Ser, from high molecular weight kininogen. We have studied vascular actions of this kinin. Its affinity for recombinant B 1 and B 2 receptors is very low, as assessed by the binding competition of [ 3 H]Lys-des-Arg 9 -BK and [ 3 H]BK, respectively, but Met-Lys-BK-Ser-Ser effectively displaced a fraction of [ 3 H]enalaprilat binding to recombinant ACE. Mutant recombinant ACE constructions revealed that affinity gap between BK and Met-Lys-BK-Ser-Ser is larger for the N-terminal catalytic site than for the C-terminal one, based on competition for the substrate Abz-Phe-Arg-Lys(Dnp)-Pro-OH in an enzymatic assay. Met-Lys-BK-Ser-Ser is a low potency stimulant of the rabbit aorta (bioassay for B 1 receptors), but the human isolated umbilical vein, a contractile bioassay for the B 2 receptors, responded to Met-Lys-BK-Ser-Ser more than expected from the radioligand binding assay, this agonist being ∼30-fold less potent than BK in the vein. Venous tissue treatment with the ACE inhibitor enalaprilat reduced the apparent potency of Met-Lys-BK-Ser-Ser by 15-fold, while not affecting that of BK. In the rabbit isolated jugular vein, Met-Lys-BK-Ser-Ser is nearly as potent as BK as a contractile stimulant of endogenous B 2 receptors (EC 50 values of 16.3 and 10.5 nM, respectively), but enalaprilat reduced the potency of Met-Lys-BK-Ser-Ser 13-fold while increasing that of BK 5.3-fold. In vascular tissue, ACE assumes a paradoxical activating role for Met-Lys-BK-Ser-Ser. |
| Databáze: | OpenAIRE |
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