Cationomycin and monensin partition between serum proteins and erythrocyte membrane: consequences for Na+ and K+ transport and antimalarial activities.

Abstract:

:The ionophore properties of cationomycin and monensin were studied on human erythrocytes by measuring Na+ influx by 23Na NMR and concomitant K+ efflux by potentiometry in the presence of increasing amounts of serum. Both ion currents (Na+ or K+) decreased linearly with the reciprocal of serum amount. The serum effects on ion currents were stronger with cationomycin than with monensin. Assuming this decreased transport activity was due to drug binding to serum proteins, a partition coefficient between the protein and the membrane phase was determined for each ionophore by using a novel model. This partition coefficient is about 30 times higher for cationomycin than for monensin; the same result was obtained with purified human serum albumin, indicating that albumin may be the major ionophore binding protein of serum. In parallel, we also measured IC50 for 50% in vitro growth inhibition of Plasmodium falciparum, the agent of malaria. In the presence of increasing serum concentrations, the antimalarial activity was decreased for both ionophores. Serum effect was less severe for monensin than for cationomycin, in agreement with the weaker interaction of monensin with proteins as shown from the partition coefficient values. A correlation was established between the ion transport currents (sodium and potassium) and the IC50 measured on P. falciparum in the presence of the various concentrations of serum. The relative value of the ion transport currents (expressed as percentage of control in absence of serum) can be indicative of the ionophore unbound fraction in the medium.

journal_name

Arch Biochem Biophys

authors

Gibot S,Jeminet G,Juillard J,Gumila C,Ancelin ML,Vial H,Delort AM

doi

10.1006/abbi.1999.1101

subject

Has Abstract

pub_date

1999-03-15 00:00:00

pages

361-72

issue

2

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(99)91101-3

journal_volume

363

pub_type

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