Bradykinin regulates human colonic ion transport in vitro.
OBJECTIVE
Kinins are acknowledged as important regulators of intestinal function during inflammation; however, their effects on human intestinal ion transport have not been reported. Here, we used muscle-stripped human colonic tissue and cultured T(84)-cell monolayers to study bradykinin (BK) actions on human intestinal ion transport.


METHODS
Ion transport was measured as changes in short-circuit current (I(sc)) across colonic epithelia mounted in Ussing chambers.


RESULTS
In intact tissue, there was a distinct polarity to BK-elicited I(sc) responses. Whereas basolateral BK stimulated sustained responses (EC(50)=0.5+/-0.1 microM), those to apical BK were more rapid and transient (EC(50)=4.1+/-1.2 nM). In T(84) cells, responses to both apical and basolateral BK were similar to those seen upon apical addition to intact tissues. Cross-desensitization between apical and basolateral domains was not observed. BK-induced responses were largely due to Cl(-) secretion as shown by their sensitivity to bumetanide and removal of Cl(-) from the bathing solution. Studies using selective agonists and antagonists indicate responses to BK are mediated by B(2) receptors. Finally, responses to basolateral BK in intact tissues were inhibited by tetrodotoxin (1 microM), atropine (1 microM), capsaicin (100 microM) and piroxicam (10 microM). BK-stimulated prostaglandin (PG)E(2) release from colonic tissue.


CONCLUSIONS
BK stimulates human colonic Cl(-) secretion by activation of apical and basolateral B(2) receptors. Responses to apical BK reflect a direct action on epithelial cells, whereas those to basolateral BK are amplified by stimulation of enteric nerves and PG synthesis.
Baird
A W
AW
School of Agriculture, Food Science and Veterinary Medicine and Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
Skelly
M M
MM
O'Donoghue
D P
DP
Barrett
K E
KE
Keely
S J
SJ
D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D065094:Bradykinin B2 Receptor Antagonists; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D017615:Enteric Nervous System / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D017136:Ion Transport / Q000187:drug effects*; D043782:Receptor, Bradykinin B2 / Q000819:agonists* / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D065094:Bradykinin B2 Receptor Antagonists; D002712:Chlorides; D043782:Receptor, Bradykinin B2; D014665:Vasodilator Agents; D015232:Dinoprostone; D001920:Bradykinin