Mechanism and specificity of lanthanide series cation transport by ionophores A23187, 4-BrA23187, and ionomycin.
A23187, 4-BrA23187, and ionomycin transport several lanthanide series trivalent cations at efficiencies similar to Ca2+, when compared at cation concentrations of approximately 10(-5) M, ionophore concentrations of approximately 10(-6) M, and a pH of 7.00. Selectivity sequences and the range of relative rates are as follows: A23187, Nd3+ > La3+ > Eu3+ > Gd3+ > Er3+ > Yb3+ > Lu3+ (approximately 34-fold); 4-BrA23187, Nd3+ > Eu3+ > Gd3+ > La3+ > Er3+ > Yb3+ > Lu3+ (approximately 34-fold); ionomycin, La3+ > Yb3+ > Nd3+ > Lu3+ > Er3+ > Eu3+ > Gd3+ (approximately 4-fold). At concentrations between 9 and 250 microM, La3+ is transported by an electroneutral mechanism, predominately through mixed complexes of the type (ionophore)2La-OH (A23187 and 4-BrA23187) or (ionophore)La-OH (ionomycin), when no membrane potential is present. For all three ionophores, an induced potential of approximately 160 mV accelerates transport by approximately 50-100%. However, measured values of H+/La3+ exchange indicate that only 4-BrA23187 displays a significant electrogenic activity under these conditions. At a La3+ concentration of 17 mM, transport by all three ionophores is electroneutral and apparently occurs through complexes of type (ionophore)3La (A23187 and 4-BrA23187) or (ionophore)La-OH (ionomycin). Analysis of these patterns in a context of comproportionation equilibria involving the transporting species and free La3+ indicates that the species containing three ionophore molecules are formed on the membrane when aqueous phase solution conditions would strongly favor a 1:1 complex, based upon previous studies in solution. The implications of this and other findings are discussed.
Wang
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Department of Medical Biochemistry, Ohio State University, Columbus 43210, USA.
Taylor
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Pfeiffer
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D000634:Aminoquinolines; D055592:Biophysical Phenomena; D001703:Biophysics; D000001:Calcimycin / Q000031:analogs & derivatives / Q000494:pharmacology; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology*; D007811:Lanthanum / Q000493:pharmacokinetics; D008081:Liposomes; D008564:Membrane Potentials; D008674:Metals, Rare Earth / Q000493:pharmacokinetics*
D000634:Aminoquinolines; D005456:Fluorescent Dyes; D007476:Ionophores; D008081:Liposomes; D008674:Metals, Rare Earth; D000001:Calcimycin; D015759:Ionomycin; D007811:Lanthanum; C033170:4-bromo-A-23187; C035739:Quin2