Effect of compounds from Mandevilla velutina on bradykinin-mediated contractile and relaxant responses of the isolated guinea pig trachea.

ABSTRACT

This study examines the action of three putative functional bradykinin (BK) antagonists isolated from Mandevilla velutina on BK and other agonist-induced contraction or relaxation responses in intact or in epithelium-denuded strips of tracheal muscle from guinea pigs. Compound MV 8612 (8 and 16 microM) and MV 8610 (12 and 24 microM) caused a graded rightward displacement of BK dose-response curves in the isolated guinea pig trachea (dose ratio 2- to 4-fold). Compound MV 8608 (28 microM) had a small effect on BK contractile responses. At high concentrations, compound MV 8612 (24 microM) caused a slight but significant depression of the BK-induced maximal responses. These pharmacological actions appear to be quite selective towards BK, since within the same concentration range these compounds failed to interfere with the sensitivities to prostaglandin F2 alpha, carbachol and histamine. However, these compounds significantly enhanced maximal responses to the latter two agonists, an action that was not influenced by indomethacin. In addition, MV 8612 and MV 8608 (16 and 56 microM) significantly potentiated BK-mediated epithelium-dependent relaxation responses in preparations precontracted with carbachol. These compounds also significantly potentiated isoprenaline but not theophylline-relaxant responses, an action that seems to occur independently of the generation of cyclooxygenase products of arachidonic acid pathway. These results further extend our previous studies and indicate that some of the M. velutina compounds exert a weak though selective antagonistic action against BK-induced contractile responses of the isolated epithelium-denuded guinea pig tracheal smooth muscle and potentiate BK-induced relaxations in tissues with intact epithelium precontracted with carbachol.(ABSTRACT TRUNCATED AT 250 WORDS)