Inhibition by nitrendipine of 86Rb+ fluxes in subconfluent MDCK cells.
Part of the natriuretic mechanism of dihydropyridine Ca2+ channel antagonists involves the inhibition of renal tubular sodium reabsorption. To identify the membrane ion transport system involved in this natriuretic action, we tested nitrendipine on unidirectional 86Rb+ fluxes in Madin-Darby canine kidney (MDCK) cells. To dissect between direct and indirect effects (via cytosolic Ca2+) of nitrendipine, the compound was re-examined on ion fluxes in human erythrocytes. In MDCK cells, external Ca2+ (3 mM), adrenalin (100 microM) and the Ca2+ ionophore A23187 (20 microM) strongly and transiently stimulated 86Rb+ efflux. All these stimulatory actions were fully inhibited by quinine (1 mM) suggesting that they reflect the opening of Ca(2+)-sensitive K+ channels. Nitrendipine was able to inhibit these Ca(2+)-sensitive K+ channels, bit this inhibitory action required concentrations of the compound (approximately 100 microM). Regarding 86Rb+ influx, the most significant result with nitrendipine was a partial inhibition of bumetanide-sensitive 86Rb+ influx. This effect represented a maximal flux inhibition of about 70% and required very low nitrendipine concentrations (IC50 approximately 1 nM). The Ca2+ ionophore A 23187 strongly stimulated bumetanide-sensitive 86Rb+ influx in MDCK cells. Conversely, a very important reduction (approximately 79%) of this influx component was found in Ca2+ depleted cells. In human red blood cells, Na+, K+, Cl- cotransport fluxes were resistant to nitrendipine, even at high concentrations of the compound (100-500 microM). Conversely, Ca(2+)-sensitive K+ channels were inhibited by nitrendipine with IC50 = 6 +/- 3 microM (mean +/- S.E.M., n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)
López-Burillo
S
S
Department of Biochemistry, School of Medicine, University of Valladolid, Spain.
Agapito-Serrano
M T
MT
Garay
R P
RP
Macías
J F
JF
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D009568:Nitrendipine / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology; D012413:Rubidium / Q000378:metabolism*
D000001:Calcimycin; D009568:Nitrendipine; D011803:Quinine; D012413:Rubidium; D002118:Calcium; D004837:Epinephrine