Induction of bradykinin B1 receptors in rat colonic epithelium.
1. Des-Arg9 bradykinin (DAB), a classical B1-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). 2. 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 EC50 for DAB was approximately 50 nM. 3. An inhibitor of transcription (actinomycin D) and of translation (cycloheximide) prevented the appearance of DAB sensitivity without affecting the responses to another secretagogue (forskolin). 4. The classical B1-kinin receptor antagonist, Leu8-des-Arg9 bradykinin, was shown to be an agonist in rat colon epithelium. Other B1-kinin receptor antagonists (des-Arg10-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. 5. 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. 6. The differences between the responses of the colonic epithelium to B1- and B2-kinin receptor agonists are discussed.
Teather
S
S
Department of Pharmacology, University of Cambridge.
Cuthbert
A W
AW
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D066298:In Vitro Techniques; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018002:Receptors, Bradykinin / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects
D065168:Bradykinin Receptor Antagonists; D018118:Chloride Channels; D011500:Protein Synthesis Inhibitors; D018002:Receptors, Bradykinin; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C024626:bradykinin, des-Arg(9)-; D003609:Dactinomycin; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D003513:Cycloheximide; D001920:Bradykinin