The kinin B₁ receptor antagonist des‐Arg⁹‐[Leu⁸]bradykinin: an antagonist of the angiotensin AT₁ receptor which also binds to the AT₂ receptor

Abstract

1 Agonists and antagonists of kinin B1 and B2 receptors were evaluated in vitro for their effects against angiotensin II (AII)-induced contractile responses in the rabbit aorta and for their binding properties to angiotensin AT1 and AT2 receptors from purified membrane of rat liver and lamb uterus respectively.2 In aortic rings, the kinin B1 receptor antagonist, des-Arg9-[Leu8]bradykinin (BK) (3-100 J4M) caused a concentration-dependent decrease in sensitivity and a depression of the maximum response to All.Des-Arg'0-[Leulkallidin (KD), des-Arg9-BK, des-Arg'°-KD, BK or KD at 3 fLM had no effect against All-induced contractions.

Haemodynamic and cardiac effects of kinin B1 and B2 receptor stimulation in conscious instrumented dogs

“…This may suggest that the B1 receptor antagonist possesses a partial agonist activity in the dog vasculature which however is absent in most of the B. receptor systems so far described (Marceau, 1995). Another explanation could be related to the recently described property of des-Arg9-[Leu8]-BK of antagonizing the effect of angiotensin II on AT1 receptors (Pruneau et al, 1995a). Such a property could explain the hypotensive response obtained with des-Arg9-[Leu8]-BK infusion, since the non-peptide angiotensin II antagonist, losartan, has been shown to induce a dose-dependent decrease in blood pressure when administered i.v.…”

The Chemistry and Biological Activities of Peptides from Amphibian Skin Secretions

“…Phypo Xa is a canonical peptide with typical pyroglutamyl (Pyr)/proline-rich classical motif sequences at the C-terminus that potentiate BK activity in vivo and in vitro and efficiently competitively inhibit angiotensin-converting enzymes . Des (Arg 9 , Leu 8 ) bradykinin is a potent BK B1 receptor antagonist . Odorranaopin (DYTIRTRLHQESSRKVL) inhibits the contractile effect induced by BK, possibly by blockade of BK or BK receptor functions .…”