The bradykinin B2 receptor antagonist icatibant (Hoe 140) blocks aminopeptidase N at micromolar concentrations: off-target alterations of signaling mediated by the bradykinin B1 and angiotensin receptors.

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Citation

Bawolak MT, Fortin JP, Vogel LK, Adam A, Marceau F

The bradykinin B2 receptor antagonist icatibant (Hoe 140) blocks aminopeptidase N at micromolar concentrations: off-target alterations of signaling mediated by the bradykinin B1 and angiotensin receptors.

Eur J Pharmacol. 2006 Dec 3;551(1-3):108-11. Epub 2006 Sep 8.

PubMed ID
17026984 [ View in PubMed
]
Abstract

The N-terminal sequence of icatibant, a widely used peptide antagonist of the bradykinin B(2) receptors, is analogous to that of other known aminopeptidase N inhibitors. Icatibant competitively inhibited the hydrolysis of L-Ala-p-nitroanilide by recombinant aminopeptidase N (K(i) 9.1 microM). In the rabbit aorta, icatibant (10-30 microM) potentiated angiotensin III, but not angiotensin II (contraction mediated by angiotensin AT(1) receptors), and Lys-des-Arg(9)-bradykinin, but not des-Arg(9)-bradykinin (effects mediated by the bradykinin B(1) receptors), consistent with the known susceptibility of these agonists to aminopeptidase N. At concentrations possibly reached in vivo (e.g., in kidneys), icatibant alters physiological systems different from bradykinin B(2) receptors.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
IcatibantAminopeptidase NProteinHumans
Unknown
Inhibitor
Details