Acetylcholine and kinin augmentation of Cl- secretion stimulated by prostaglandin in a canine renal epithelial cell line.
1. The actions of kinins and of acetylcholine upon transepithelial ion transport in a renal-derived cultured epithelium (Madin-Darby canine kidney cells, MDCK) have been investigated. 2. In voltage-clamped epithelial layers mounted in Ussing chambers and with prior stimulation of inward short-circuit current (SCC) by 5 or 10 microM-prostaglandin E1 (PGE1), both bradykinin (1 microM) and acetylcholine (0.1 mM) stimulate an additional, but transient, inward SCC. In the absence of PGE1 minimal effects of both bradykinin and acetylcholine upon SCC are observed. The SCC response to bradykinin and acetylcholine are attenuated with prior stimulation by 10 microM-adrenaline. 3. Measurements of bradykinin and acetylcholine-stimulated inward SCC with cation and anion replacement of the bathing media and the use of the Cl channel blocker 5-nitro-2(3-phenylpropylamino)-benzoic acid (NPPB) together with bumetanide to inhibit Na(+)-K(+)-Cl- 'co-transport', are consistent with the bradykinin- and acetylcholine-stimulated SCC being the result of basal to apical Cl- secretion. 4. Bradykinin (1 microM) is capable of stimulation of inward SCC from both epithelial surfaces, whilst acetylcholine is only effective from the basolateral surface. Kallidin (lys-bradykinin) was similar in effect to bradykinin from both epithelial surfaces whereas bradykinin (1-8) was ineffective, suggesting that B2 bradykinin receptors mediate the effect of bradykinin upon SCC. Dose-response relationships show that the response to kallidin and bradykinin was of higher sensitivity for additions to the apical cell aspects. 5. The data are discussed in relation to a model for epithelial Cl- secretion, and to the mechanism of natriuresis observed with kinins and acetylcholine in vivo.
Simmons
N L
NL
Department of Physiological Sciences, Medical School, University of Newcastle upon Tyne.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002460:Cell Line / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D004848:Epithelium / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects
D002712:Chlorides; D007473:Ion Channels; D015232:Dinoprostone; D000109:Acetylcholine; D001920:Bradykinin