Analysis of the antagonistic actions of HOE 140 and other novel bradykinin analogues on the guinea-pig ileum.
The type of antagonism exhibited by three novel bradykinin (BK) antagonists, D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]BK (HOE 140, compound I), D-Arg-[Hyp3,D-Tic7,Oic8]BK (compound II) and [Arg(Tos)1,Hyp3,Thi5,D-Tic7,Oic8]BK (compound III), was compared with that of a conventional antagonist, D-Arg-[Hyp2,Thi5,8,D-Phe7]BK (compound IV), on the guinea-pig ileum. The novel compounds induced rightward displacements of cumulative concentration-response curves to BK, accompanied by a progressive reduction of the maximum effect (Emax) without a significant decrease in the slope, whereas no reduction of Emax was observed with compound IV. Actions of substance P on the guinea-pig ileum and of vasopressin on the rat uterus remained completely unaffected. It is concluded that as the novel BK analogues show competitive as well as non-competitive inhibition in the guinea-pig ileum, but the inhibition is reversible and specific, they are dual antagonists.
Griesbacher
T
T
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Lembeck
F
F
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*
D009842:Oligopeptides; C065679:icatibant; D001920:Bradykinin