Solute-induced acceleration of transbilayer movement and its implications on models of blood-brain barrier

Jain, Mahendra Kumar; Jahagirdar, D.V.; Linde, Mona; Roelofsen, B.; Eibl, Hansjörg

doi:10.1016/0005-2736(85)90010-0

Cited by 19 publications

(8 citation statements)

References 30 publications

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“…Thus, it is the liquid crystalline state of the liposomal membrane, but not the chemical structure of lipid alkyl chains, that is critical for realizing flip-flop. It has been shown earlier that flip-flop can be activated by specific enzymes [46,47], non-ionic amphiphilic polymers [48,49] and low molecular weight substances [50][51][52][53][54]. We now demonstrate that flexible synthetic cationic polymers are capable of inducing a similar "flippase" effect.…”

Section: Binding Of Conventional Cationic Polymers To Small Liquid Anmentioning

confidence: 73%

Polyelectrolyte-coated liposomes: Stabilization of the interfacial complexes

Yaroslavov¹,

Rakhnyanskaya²,

Yaroslavova³

et al. 2008

Advances in Colloid and Interface Science

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Section: Binding Of Conventional Cationic Polymers To Small Liquid Anmentioning

confidence: 73%

Polyelectrolyte-coated liposomes: Stabilization of the interfacial complexes

Yaroslavov¹,

Rakhnyanskaya²,

Yaroslavova³

et al. 2008

Advances in Colloid and Interface Science

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“…The passive transbilayer movement of the chromophoric Pgp-substrate, rhodamine 123 (19), and quinine, an MDR modulator, was determined by essentially the method of Jain et al (22), which follows transbilayer movement of a hydrophobic peptide. The transfer of rhodamine 123 from the aqueous phase to the bilayer of artificial lipid vesicles is accompanied by quenching of its fluorescence.…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, valinomycin is a cyclic carrier-type peptide ionophore with a uniform hydrophobic surface and is freely soluble in biological membranes. Although, both valinomycin and gramicidin D are soluble in organic solvents, valinomycin traverses the membrane at least 25 ϫ 10 4 times s Ϫ1 , i.e., with a lifetime of microseconds (22), whereas gramicidin D flip-flops across the membrane with a lifetime of minutes (23).…”

Section: Discussionmentioning

confidence: 99%

“…The transbilayer movement rate of these substrates had been determined by transport studies taking advantage of their function as ionophores, and thus we examined their ability to modulate Pgp-mediated drug efflux. Valinomycin is a mobile carrier that is freely soluble in the membrane (22), whereas gramicidin D is a channel-forming ionophore with a slow transbilayer flip-flop (23). The ability of these ionophores to modulate Pgp function was tested using the assay of calcein-AM efflux inhibition in Emt R1 cells, essentially as described by Holló et al (20).…”

Section: Table I Solubility and Binding Properties Of Drugs And Modulmentioning

confidence: 99%

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The Role of Passive Transbilayer Drug Movement in Multidrug Resistance and Its Modulation

Eytan

Regev

Oren

et al. 1996

Journal of Biological Chemistry

172

121

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The successful lowering of the intracellular concentration of multidrug resistance (MDR)-type drugs by P-glycoprotein (Pgp) relies on its ability to overcome the passive influx rate of each MDR-type drug. Thus, the aim of the present work was to study the effect of passive transbilayer drug movement on the multidrug resistance and its modulation. Fluorescence quenching studies indicated that whereas the Pgp substrate rhodamine 123 traverses an artificial lipid membrane with a lifetime of 3 min, the transbilayer movement rate of the MDR modulators, quinidine and quinine, was too fast to be detected with present methods. Transbilayer movement rates of drugs and modulators were estimated from their equilibration rate throughout artificial multilamellar vesicles. The equilibration rate of five selected modulators was faster than the equilibration rate of five representative MDR-type drugs tested, which was comparable with the rate of rhodamine 123 equilibration. Moreover, the carrier-type peptide ionophore, valinomycin, which is freely mobile in the membrane, inhibited Pgp-mediated efflux of rhodamine 123 from MDR cells. In contrast, the channel-forming ionophore gramicidin D, a Pgp substrate that flip-flops slowly across the membrane, did not modulate cellular Pgp activity. Pgp, with a turnover number of about 900 min-1 can keep pace with the influx of an MDR-drug like rhodamine 123 exhibiting a transbilayer movement with a lifetime of minutes. On the other hand, Pgp would fail to protect MDR cells against cytotoxic drugs that are freely mobile through biological membranes and that re-enter cells faster than their Pgp-mediated active efflux rate. The relatively fast transbilayer movement exhibited by MDR modulators suggest that in contrast to MDR-type drugs, MDR modulators traverse the plasma membrane faster than the maximal expulsion rate of Pgp.

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“…Infusion of alkylglycerol compounds into the carotid territory produces experimental openings (Erdlenbruch et al, 2000(Erdlenbruch et al, , 2003a of a magnitude comparable to C10 or osmotic treatment, and possibly by a distinctly different mechanism. While evidence for tight junction opening by alkylglycerol infusion has been reported (Erdlenbruch et al, 2003a), it is also thought that these compounds incorporate into the endothelial membrane, causing temporary disorganization of the lipid bilayer and its fluidization in a manner facilitating trans-endothelial incorporation and diffusion of molecules (Erdlenbruch et al, 2000;Jain et al, 1985). An argument favoring development and use of this method is that the degree and duration of opening are readily controllable, being determined by choice of alkylglycerol, concentration and dose rate, and that is superior to osmotic opening in this respect (Erdlenbruch et al, 2003b).…”

Section: Discussionmentioning

confidence: 98%