Receptors and mechanisms mediating the biphasic response evoked by bradykinin in rat colonic smooth muscle

In rat duodenum, bradykinin induces a relaxation followed by a contraction. Different types of ion channels and receptors as well as non-muscle cells have been suggested to be involved in this response. As it is unclear whether these changes are observed also in rat large intestine and the mechanisms which might underlie this response, the effect of bradykinin on rat colonic motility was tested.

Isometric contractions were measured on full-thickness preparations or preparations, from which individual layers had been dissected. The expression of bradykinin receptors was analyzed by immunohistochemistry and RT-PCR. Isolated intestinal muscle cells were investigated with Ca(2+) -imaging techniques.

Bradykinin caused a biphasic contractile response (initial relaxation followed by contraction) in rat colon, which was resistant against tetrodotoxin. The kinin-induced relaxation was inhibited by tetrapentylammonium chloride, a blocker of Ca(2+) -activated K(+) channels. Des-arg(9) -bradykinin did not induce any effect on the native colon, although after 5 h in vitro preincubation, a contractile response was evoked by this B1 receptor agonist. The consecutive ablation of adherent layers of the intestinal wall strongly reduced the response to bradykinin in comparison with a control stimulus, i.e., carbachol, suggesting a contribution of non-muscle cells in the mediation of this response.

Bradykinin induced a biphasic change in contractility in the rat colon. In the native intestine, only the B2 receptor is involved in this effect. Neighboring cell obviously sensitize the smooth muscle to the stimulation of these receptors.