Application of drug receptor theories to the analysis of the myotropic effects of bradykinin.
Cat jejunum and terminal ileum, and rat stomach strip and rat uterus contract to bradykinin, while rat duodenum relaxes. Dose-response curves of classical hyperbolic shape are obtained in the first three preparations, but not in the others. The negative logs of the drug concentrations which give 50% of the maximal response. (pD2) Values were, respectively, 7.68 and 7.77 in the cat jejunum and terminal ileum, 6.78 in the rat stomach strip and 8.64 in the rat uterus in estrus. Theoretical dose-response curves, constructed by using experimental pD2 values in the equation of Clark, (General pharmacology. Verlag Van J. Springer, Berlin, 1937), are superimposed to experimental curves, obtained in the cat jejunum and terminal ileum, but not in the rat stomach strip. This comparison was not made in the rat uterus and duodenum. The myotropic effect of bradykinin appears to be a direct one in the cat jejunum, the terminal ileum and the rat stomach strip, because it is not affected by anticholinergics, antiadrenergics, antihistaminics and indomethacin. pD2 values and the slope of the dose-response curves of the rat uterus were reduced by indomethacin. The results indicate that cat jejunum and terminal ileum are sensitive and specific for bradykinin and appear to be the most reliable preparations for studies on the structure-activity relationships of this peptide.
D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007583:Jejunum / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D011955:Receptors, Drug; D013270:Stomach / Q000187:drug effects; D013329:Structure-Activity Relationship; D013565:Sympatholytics / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects
D006634:Histamine H1 Antagonists; D010276:Parasympatholytics; D011955:Receptors, Drug; D013565:Sympatholytics; D001920:Bradykinin; D007213:Indomethacin