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Induction of bradykinin B 1 receptors in rat colonic epithelium
Author(s) -
Teather Sarah,
Cuthbert Alan W
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701225
Subject(s) - endocrinology , kinin , medicine , bradykinin , cystic fibrosis transmembrane conductance regulator , agonist , receptor , epithelium , chemistry , histamine , kallidin , forskolin , receptor antagonist , biology , antagonist , cystic fibrosis , genetics
Des‐Arg 9 bradykinin (DAB), a classical B 1 ‐kinin receptor agonist was without effect when applied to the basolateral surface of rat isolated colon epithelium. Three hours after tissues were isolated DAB caused, after a delay of up to 2 min, a maintained increase of short circuit current (SCC). The SCC increase in colonic epithelia, mounted in vitro for three hours, caused by DAB was due to electrogenic chloride secretion as the current increase was reversed by frusemide and did not occur in the absence of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. The EC 50 for DAB was approximately 50 n M . An inhibitor of transcription (actinomycin D) and of translation (cycloheximide) prevented the appearance of DAB sensitivity without affecting the responses to another secretagogue (forskolin). The classical B 1 ‐kinin receptor antagonist, Leu 8 ‐des‐Arg 9 bradykinin, was shown to be an agonist in rat colon epithelium. Other B 1 ‐kinin receptor antagonists (des‐Arg 10 ‐Hoe 140 and R‐715) inhibited the responses to DAB in ‘aged’ colonic epithelia, and the inhibition was easily surmounted by increasing the concentration of DAB. Response to DAB did not appear to involve to any significant extent, the formation of prostaglandins, leukotrienes, histamine or nitric oxide. Furthermore, no neuronal involvement was apparent in the stripped colonic preparations. The responses to DAB were not significantly different in epithelia taken from different parts of the distal colon. The differences between the responses of the colonic epithelium to B 1 ‐ and B 2 ‐kinin receptor agonists are discussed.