Kinins as mediators of intestinal secretion.
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.
Gaginella
T S
TS
Department of Internal Medicine, College of Medicine, Ohio State University, Columbus 43210-1228.
Kachur
J F
JF
D000818:Animals; D002712:Chlorides / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D007410:Intestinal Diseases / Q000503:physiopathology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000294:innervation / Q000502:physiology*; D007705:Kinins / Q000502:physiology*; D008084:Lipoxygenase / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000502:physiology
D002712:Chlorides; D005609:Free Radicals; D007705:Kinins; D011453:Prostaglandins; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D008084:Lipoxygenase; D010100:Oxygen