The effects of membrane lipid order and cholesterol on the internal and external cationic sites of the   pump in erythrocytes

Giraud, Françoise; Claret, M; Bruckdorfer, K. Richard; Chailley, Bernadette

doi:10.1016/0005-2736(81)90253-4

Cited by 107 publications

(42 citation statements)

References 31 publications

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“…Thus, the leaflet into which CPZ preferentially distributes is the same as that in which we propose FC interacts with the drug transporter (Table 1; Figure 4). Differential effects by CPZ on pump activity have been demonstrated for the Na + /K + -ATPase: CPZ was found to alter the affinity and the translocation rate of cations interacting with the pump at the internal cationic site, whilst having no effect on cations binding at the external cationic site (Giraud et al, 1981). CPZ has been found to inhibit allosterically [ 3 H]VLB transport in inside-out membrane vesicles (Syed et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Selective modulation of P-glycoprotein-mediated drug resistance

2001

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Multidrug resistance associated with the overexpression of the multidrug transporter P-glycoprotein is a serious impediment to successful cancer treatment. We found that verapamil reversed resistance of CEM/VLB 100 cells to vinblastine and fluorescein-colchicine, but not to colchicine. Chlorpromazine reversed resistance to vinblastine but not to fluorescein-colchicine, and it increased resistance to colchicine. Initial influx rates of fluorescein-colchicine were similar in resistant and parental cells, whereas vinblastine uptake was about 10-fold lower in the resistant cells. These results provide indirect evidence that fluorescein-colchicine is transported from the inner leaflet of the membrane and vinblastine from the outer membrane leaflet. Verapamil inhibited fluorescein-colchicine transport in inside-out vesicles made from resistant cells, whilst chlorpromazine was found to activate the transport of fluorescein-colchicine. The chlorpromazine-induced activation of fluorescein-colchicine transport was temperature-dependent and may reflect its interaction with phospholipids localised in the same bilayer leaflet. Conversely, chlorpromazine localisation in this leaflet may be responsible for its allosteric inhibition of vinblastine transport from the opposing membrane leaflet. The proposed relationship between the selectivity of modulation of P-glycoprotein and the membrane localisation of the cytotoxic drug substrates and modulators may have important implications in the rational design of regimes for the circumvention of multidrug resistance clinically. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionmentioning

confidence: 99%

Selective modulation of P-glycoprotein-mediated drug resistance

2001

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Section: Discussionmentioning

confidence: 99%

True

2001

Br J Cancer

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“…In addition, it has been reported to inhibit NA+/K+-ATPase, a membrane-bound enzyme which is sensitive to changes in physical membrane state [31], in lymphocytes [32]. These findings raise the question of whether CsA inhibits 02 formation through alterations in physical membrane properties.…”

Section: Discussionmentioning

confidence: 99%

Evidence that inhibition of phorbol ester-induced superoxide anion formation by cyclosporin a in phagocytes is not mediated by direct inhibition of protein kinase C

Wenzel-Seifert

Schächtele²,

Hummel³

et al. 1994

Biochemical Pharmacology

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Abstraet--Cyclosporin A (CsA) has been reported to inhibit phorbol myristate acetate (PMA)-induced superoxide anion (02) formation in human neutrophils and murine macrophages. We found that CsA inhibited 02 formation in HL-60 cells induced by PMA (30 nM) and phorbol dibutyrate (200 nM) with a half-maximal effect at 1 and 0.75 pM, respectively. One possible target of CsA action is protein kinase C (PKC) [EC 2.7.1.37] since phorbol esters activate this kinase. However, CsA did not inhibit PMAmediated reduction of histamine-induced rises in cytosolic Ca 2+ concentration in, and PMA-induced differentiation of, HL-60 cells and platelet aggregation. CsA did not reduce the activity of various recombinant c-PKC isoenzymes (o~,/31 and 7), n-PKC isoenzymes (6 and e), an a-PKC isoenzyme (~) nor of PKC purified from rat brain in vitro. These data show that CsA inhibits phorbol ester-induced O2 formation in HL-60 cells but not other phorbol ester-mediated events and that inhibition by CsA of O2 formation cannot readily be attributed to direct PKC inhibition. We also show that CsA does not change the activity of nucleoside diphosphate kinase ]EC 2.7.4.6] in HL-60 membranes nor the latter's physical properties.

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The effects of membrane lipid order and cholesterol on the internal and external cationic sites of the pump in erythrocytes

Cited by 107 publications

References 31 publications

Selective modulation of P-glycoprotein-mediated drug resistance

Selective modulation of P-glycoprotein-mediated drug resistance

True

Evidence that inhibition of phorbol ester-induced superoxide anion formation by cyclosporin a in phagocytes is not mediated by direct inhibition of protein kinase C

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