Biological activities of kinins modified at the N- or at the C-terminal end.
A series of analogues of des-Arg9-bradykinin, modified at the N- or C-terminal end, were tested on rabbit aorta strips (receptor B1) and on cat ileum strips (receptor B2) in an attempt to find long-acting agonists and antagonists. It was found that the methylation or the amidation of the C-terminal carboxyl reduces the affinity and (only the amidation) the intrinsic activity of the agonists, while not changing significantly the duration of action of both agonists and antagonists. The addition of a Lys at the N terminal is accompanied by a marked increase of affinity, no changes of intrinsic activity, and a prolongation of the duration of action of agonists. Antagonists behave in a similar way as the agonists and show increased affinity; the time required for inducing full inhibition as well as the duration of action are significantly increased. The pharmacological and physiopathological implications of these results are discussed.
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007705:Kinins / Q000494:pharmacology*; D008745:Methylation; D009119:Muscle Contraction / Q000187:drug effects; D011817:Rabbits; D013329:Structure-Activity Relationship; D013997:Time Factors
D000577:Amides; D007705:Kinins