KININ-STIMULATED CHLORIDE SECRETION IN MOUSE COLON REQUIRES THE PARTICIPATION OF CFTR CHLORIDE CHANNELS

The effect of lysylbradykinin on electrogenic chloride secretion in th e epithelium of the mouse colon has been investigated. The peptide was active only when applied to the basolateral surface and its effects w ere inhibited by the B-2 receptor antagonist, Hoe 140, also applied to the same surface. The chloride channel blocker, niflumic acid, also i nhibited the response to kinin when added apically. Cyclo-oxygenase in hibition with piroxicam attenuated the responses to kinin, indicating involvement of prostaglandins in the responses. It is concluded that l ysylbradykinin increases chloride secretion by acting via B-2 receptor s and, as with other tissues, brings about secretion through the agenc y of multiple messengers. In colonic epithelia from cystic fibrosis (C F) mice lysylbradykinin was without effect, suggesting that the final effector process involves apically located cystic fibrosis transmembra ne conductance regulator (CFTR) chloride channels.