guanosine-triphosphate and icatibant

The type of antagonism exhibited by the potent bradykinin B2 receptor antagonist, Hoe 140, on the rat uterus was investigated using various approaches. In the isolated rat uterus the concentration-response curve of bradykinin was shifted to the right and the maximum effect was reduced after pretreatment with Hoe 140 for 5 min. Shorter times of antagonist pretreatment failed to decrease the maximum effect of bradykinin. In the [3H]BK binding assay Hoe 140 bound with pM affinity to a single site and did not discriminate multiple bradykinin receptors. Studying the bradykinin-induced G protein activation we could verify that Hoe 140 at subnanomolar concentrations selectively antagonized the low-affinity BK receptor in the rat myometrium. At nM concentrations Hoe 140 itself was able to stimulate G proteins. The results suggest that in the rat uterus, differently from guinea pig ileum, Hoe 140 possibly acts as a mixed competitive as well as functional antagonist.

Topics: Animals; Bradykinin; Dose-Response Relationship, Drug; Female; GTP-Binding Proteins; Guanosine Triphosphate; In Vitro Techniques; Myometrium; Radioligand Assay; Rats; Receptors, Bradykinin; Receptors, Neurotransmitter