Kinins are small
peptides that have diverse
biological actions. Concentrations of
kinins in the nanomolar or subnanomolar range induce intestinal smooth muscle contraction and evoke mucosal
electrolyte secretion. Hyperkininemia is associated with effects on gastrointestinal motility and intestinal mucosal
inflammation.
Bradykinin and
kallidin are the predominant
kinins with effects on the gastrointestinal tract of mammals.
Bradykinin stimulates
chloride ion secretion by the guinea pig and rabbit ileum, rabbit colon, rat colon and monolayers of human HCA-7 cells.
Kinins directly or indirectly stimulate
phospholipase A2 and
phospholipase C. Cells in the lamina propria of the mucosa (e.g., fibroblasts, mast cells, leukocytes), by liberating
cyclooxygenase and
lipoxygenase metabolites of
arachidonic acid, are involved in the
kinin response; direct effects on epithelial cells cannot be ruled out, however. Antagonists now exist for
kinin receptors. Based on studies with these antagonists in smooth muscle preparations, two subgroups of
kinin receptor have been identified. The B2-type receptor appears to be responsible for both the contraction of ileal muscle and ileal secretion.
Kinins are probably more important as pathophysiological rather than as physiological mediators. They may amplify the effect of inflammatory products that induce intestinal secretion. The precise involvement of
kinins in clinical mucosal secretory states and
diarrhea will require quantitative assessment of their levels during each phase of mucosal
inflammation. Additional studies on the mechanism of action of
kinins will be essential in designing
therapy to mitigate the symptoms associated with mucosal
inflammation.