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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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.[1]


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