Abstract
Peptide analogs of bradykinin (BK) containing unusual amino acids are potent antagonists of the actions of BK in various smooth muscle preparations. Apparent pA2 values above 7.0 could be demonstrated for Lys-Lys-[Hyp3, Thi5.8, D-Phe7]-BK (B4310) in the rat uterus and the rat duodenum. Actions of BK that are related to its possible role in inflammation could be antagonized in a specific and dose-dependent manner by B4310. Stimulation by BK of C fiber afferent neurons was investigated in the rabbit ear reflex preparation and in the isolated rabbit iris sphincter muscle. In both preparations, B4310 caused a parallel shift of the dose-response curves to BK. In the latter case, a pA2 value was established that agrees well with the values found on smooth muscles. However, the short duration of action of the antagonists suggested a rapid inactivation by peptidases.
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