Effects of bradykinin on the canine proximal colon

The canine proximal colon set up in Ussing chambers responded to the serosal addition of bradykinin (BK) with changes in short-circuit current (Isc). Two preparations were used to analyze these effects - an innervated mucosal preparation and a 'functionally nerve-free' epithelial preparation. The specific questions that this study sought to answer were (1) is there a significant neural component to the effects noted?, and (2) what is the receptor subtype involved? BK produced dose-dependent increases across both the mucosa and the epithelial preparations. A secondary decrease in Isc was noted in the mucosal but not the epithelial preparation. Tetrodotoxin (TTX) significantly inhibited the magnitude of mucosal responses and delayed their onset as well, indicating the presence of a significant neural component. Addition of the B2 antagonist, D-Arg0[Hyp3,Thi5,8, D-Phe7]BK produced a surmountable inhibition of the responses to the agonist. The B1 selective agonist, des-Arg9BK produced increases in Isc across both preparations, though TTX had no significant effects on these responses. Cross-desensitization was seen between BK and des-Arg9 BK. However, since the B1 selective antagonist, des-Arg9[Leu8]BK acted as a partial agonist in our preparation, these effects could not be defined further. Clearly, B2 receptors are involved in mediating canine colonic BK responses, however the role of B1 receptors in this tissue requires further definition.