title: The primary and final effector mechanisms required for kinin-induced epithelial chloride secretion.
abstract: The short-circuit current technique was used to examine the effects of N2-L-lysylbradykinin (LBK) on chloride secretion in the mucosae of the 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 mammals, with 2 nM being sufficient to cause half-maximal secretion. The 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 CF gene into the genome of CF null mice at the zygote stage restored the chloride secretory activity of LBK, with only minor differences in potency. In mice in which the kinin B2 receptor gene had been disrupted, LBK had no effect, whereas the responses to forskolin were unchanged. Thus the acute effects of kinins on chloride secretion depend uniquely on kinin B2 receptors and CFTR chloride channels, which form the primary and final effector mechanisms of the secretory process.
authors.affiliation: Department of Pharmacology, University of Cambridge, United Kingdom.
authors.forename: A W
authors.initials: AW
authors.lastname: Cuthbert
authors.forename: C
authors.initials: C
authors.lastname: Huxley
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D018244:Chromosomes, Artificial, Yeast; D005576:Colforsin / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007609:Kallidin / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D005576:Colforsin; D007609:Kallidin