Ca2+ channel inhibition in a rat osteoblast-like cell line, UMR 106, by a new dihydropyridine derivative, S11568
P Morain, JL Peglion, E Giesen-Crouse - European journal of …, 1992 - Elsevier
P Morain, JL Peglion, E Giesen-Crouse
European journal of pharmacology, 1992•ElsevierUMR 106 rat osteogenic sarcoma cells were studied with the whole cell patch clamp
technique to investigate the presence of voltage-gated inward currents. In barium (Ba 2+)-
containing medium, depolarizing jumps revealed both transient (T-type) and sustained (L-
type) Ba 2+ currents. The L-type component was dihydropyridine-sensitive: the agonist Bay
K 8644 increased the amplitude of the L-type Ba 2+ current. A new dihydropyridine calcium
channel blocker, S 11568 ((±)-2-{2-[2-(aminoethoxy) ethoxyl] methyl} 4-(2′, 3 …
technique to investigate the presence of voltage-gated inward currents. In barium (Ba 2+)-
containing medium, depolarizing jumps revealed both transient (T-type) and sustained (L-
type) Ba 2+ currents. The L-type component was dihydropyridine-sensitive: the agonist Bay
K 8644 increased the amplitude of the L-type Ba 2+ current. A new dihydropyridine calcium
channel blocker, S 11568 ((±)-2-{2-[2-(aminoethoxy) ethoxyl] methyl} 4-(2′, 3 …
Abstract
UMR 106 rat osteogenic sarcoma cells were studied with the whole cell patch clamp technique to investigate the presence of voltage-gated inward currents. In barium (Ba2+)-containing medium, depolarizing jumps revealed both transient (T-type) and sustained (L-type) Ba2+ currents. The L-type component was dihydropyridine-sensitive: the agonist Bay K 8644 increased the amplitude of the L-type Ba2+ current. A new dihydropyridine calcium channel blocker, S 11568 ((±)-2-{2-[2-(aminoethoxy)ethoxyl]methyl}4- (2′,3′-dichlorophenyl)3-ethoxycarbonyl-5-methoxycarbonyl-6-methyl-1,4-dihydropyridine, and its enantiomers, S 12967 ((+)-S 11568) and S 12968 ((−)-S 11568), inhibited the L-type Ba2+ current. IC50 values at a holding potential (VH) of −50 mV were 90 nM for S 11568, 800 nM for S 12967 and 45 nM for S 12968. At VH = −80 mV, S 12968 was less potent (IC50 near 500 nM). In contrast, S 12968 was without appreciable effect on the T-type component of the inward current through Ca2+ channels. Our results indicate that UMR 106 cells express both T-type and L-type Ca2+ channels and could be used to study the modulation by Ca2+ channel blocking agents, such as S 12968, of the hormonal regulation of Ca2+ fluxes across the osteoblast membrane.
Elsevier