EFFECTS OF BRADYKININ ON THE CANINE PROXIMAL COLON

The canine proximal colon set up in Ussing chambers responded to the s erosal addition of bradykinin (BK) with changes in short-circuit curre nt (Isc). Two preparations were used to analyze these effects - an inn ervated 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-depe ndent increases across both the mucosa and the epithelial preparations . A secondary decrease in Isc was noted in the mucosal but not the epi thelial preparation. Tetrodotoxin (TTX) significantly inhibited the ma gnitude of mucosal responses and delayed their onset as well, indicati ng the presence of a significant neural component. Addition of the B2 antagonist, D-Arg0[Hyp3, Thi5,8, D-Phe7]BK produced a surmountable inh ibition 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 a ntagonist, des-Arg9[Leu8]BK acted as a partial agonist in our preparat ion, these effects could not be defined further. Clearly, B2 receptors are involved in mediating canine colonic BK responses, however the ro le of B1 receptors in this tissue requires further definition.