THE PRIMARY AND FINAL EFFECTOR MECHANISMS REQUIRED FOR KININ-INDUCED EPITHELIAL CHLORIDE SECRETION

The short-circuit current technique was used to examine the effects of N-2-L-lysylbradykinin (LBK) on chloride secretion in the mucosae of t he mouse intestine. It was found to be a potent chloride secretagogue in the mucosa lining the colon, jejunum, and cecum, as it is in most m ammals, with 2 nM being sufficient to cause half-maximal secretion. Th e extent of the responses was in the order cecum > colon > jejunum. In cystic fibrosis (CF) null mice, with no CF transmembrane conductance regulator (CFTR) chloride channels, LBK caused no chloride secretion, but transporting activities for other ions were revealed. Introduction of the human C-F gene into the genome of CF null mice at the zygote-s tage restored the chloride secretory activity of LBK, with only minor differences in potency In mice in which the kinin B-2 receptor gene ha d been disrupted, LBK had no effect, whereas the responses to forskoli n were unchanged. Thus the acute effects of kinins on chloride secreti on depend uniquely on kinin B-2 receptors and CFTR chloride channels, which form the primary and final effector mechanisms of the secretory process.