Site and mechanisms of action of kinins in rat ileal mucosa

Kinin-induced secretion in the intestine is accompanied by marked increases in mucosal adenosine 3',5'-cyclic monophosphate (cAMP) and prostanoids that undoubtedly contribute to the overall secretory responses. The authors have investigated the effects of kallidin on the phospholipase-prostanoid-cAMP pathway in whole ileal mucosa and in epithelial cells isolated from the same tissue in the rat. Kallidin (1 μM) stimulated a marked rise in PG (prostaglandin) E2 release from the serosal surface of stripped ileal mucosa within 1-2 min, which correlated closely with the rise in mucosal short-circuit current. Mucosal cAMP levels were also increased two to threefold by kallidin. However, kinins were unable to elicit effects under the same conditions in suspensions of viable epithelial cells. PGE2 release was unaffected by kallidin or bradykinin at concentrations up to 100 μM, whereas cAMP levels could be stimulated by forskolin and PGE2 but not by kinin. Studies of intestinal phospholipase A2 (PLA2) activity also suggest a nonepithelial site for kinin action. In the intestine, PLA2 activity was found to be concentrated within the subepithelium with significantly lower levels in the epithelium itself. In addition, kallidin was unable to influence phospholipid labeling (an indirect measure of PLA2 activity) in cells incubated with [14C] arachidonic acid. These studies suggest that kinins initiate increases in intestinal prostaglandin and cAMP production within the subepithelium and not by a direct action on epithelial cells