Stereoselective, SH-dependent transfer of lactate in mammalian erythrocytes

Deüticke, B.; Rickert, I.; Beyer, Eric C.

doi:10.1016/0005-2736(78)90381-4

Cited by 117 publications

(85 citation statements)

References 54 publications

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“…7D we demonstrate that erythrocytes from rodents (rats, guinea pigs, and hamsters) contain mainly gp70, whereas in rabbit erythrocytes, as found by others (34), there is a large amount of CD147, but little gp70. Bovine erythrocytes express neither, but it is also known that they do not express any monocarboxylate transporter (35,36). Rates of lactate transport were found to be faster in rabbit than rat erythrocytes and were much more sensitive to inhibition by 0.2 mM pCMBS treatment (Fig.…”

Section: Fig 6 the Ancillary Protein For Mct2 Is Gp70mentioning

confidence: 93%

Basigin (CD147) Is the Target for Organomercurial Inhibition of Monocarboxylate Transporter Isoforms 1 and 4

Wilson

Meredith

Fox

et al. 2005

Journal of Biological Chemistry

260

285

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Translocation of monocarboxylate transporters MCT1 and MCT4 to the plasma membrane requires CD147 (basigin) with which they remain tightly associated. However, the importance of CD147 for MCT activity is unclear. MCT1 and MCT4 are both inhibited by the cellimpermeant organomercurial reagent p-chloromercuribenzene sulfonate (pCMBS). Here we demonstrate by site-directed mutagenesis that removal of all accessible cysteine residues on MCT4 does not prevent this inhibition. pCMBS treatment of cells abolished co-immunoprecipitation of MCT1 and MCT4 with CD147 and enhanced labeling of CD147 with a biotinylated-thiol reagent. This suggested that CD147 might be the target of pCMBS, and further evidence for this was obtained by treatment of cells with the bifunctional organomercurial reagent fluorescein dimercury acetate that caused oligomerization of CD147. Site-directed mutagenesis of CD147 implicated the disulfide bridge in the Ig-like C2 domain of CD147 as the target of pCMBS attack. MCT2, which is pCMBS-insensitive, was found to co-immunoprecipitate with gp70 rather than CD147. The interaction between gp70 and MCT2 was confirmed using fluorescence resonance energy transfer between the cyan fluorescent protein-and yellow fluorescent proteintagged MCT2 and gp70. pCMBS strongly inhibited lactate transport into rabbit erythrocytes, where MCT1 interacts with CD147, but not into rat erythrocytes where it interacts with gp70. These data imply that inhibition of MCT1 and MCT4 activity by pCMBS is mediated through its binding to CD147, whereas MCT2, which associates with gp70, is insensitive to pCMBS. We conclude that ancillary proteins are required to maintain the catalytic activity of MCTs as well as for their translocation to the plasma membrane.

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Section: Fig 6 the Ancillary Protein For Mct2 Is Gp70mentioning

confidence: 93%

Basigin (CD147) Is the Target for Organomercurial Inhibition of Monocarboxylate Transporter Isoforms 1 and 4

Wilson

Meredith

Fox

et al. 2005

Journal of Biological Chemistry

260

285

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“…Lactate RBC transport has been demonstrated to be due to three distinct mechanisms: transport by MCT1, transport by the anion exchanger, AE1 or band 3, and passive diffusion, which is demonstrated to be minimal . At physiologic lactate concentrations, MCT-mediated transport has been identified as the primary mode of lactate transport across human and rat RBC membranes, with band 3-mediated transport being prominent at very high (Ͼ300 mM) lactate concentrations (Deuticke et al, 1978Poole and Halestrap, 1993). GHB is a known MCT substrate; however, transport by band 3 has not been previously evaluated, and the relative contribution of these transporters to GHB transport across the RBC membrane is not known.…”

Section: Introductionmentioning

confidence: 99%

γ-Hydroxybutyrate Blood/Plasma Partitioning: Effect of Physiologic pH on Transport by Monocarboxylate Transporters

Morse

Felmlee²,

Morris³

2011

Drug Metab Dispos

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ABSTRACT:The drug of abuse ␥-hydroxybutyrate (GHB) displays nonlinear renal clearance, which has been attributed to saturable renal reabsorption by monocarboxylate transporters (MCTs) present in the kidney. MCT1 is also present in red blood cells (RBCs); however, the significance of this transporter on the blood/plasma partitioning of GHB is unknown. The purpose of this research was to characterize the transport of GHB across the RBC membrane and assess GHB blood/plasma partitioning in vivo in the presence and absence of a competitive MCT inhibitor, L-lactate. In vitro experiments were performed using freshly isolated rat erythrocytes at pH values of 6.5 and 7.4. Inhibition with p-chloromercuribenzene sulfonate and 4,4-diisothiocyanostilbene-2,2-disulfonate were used to determine the contribution of MCT1 and band 3, respectively, on GHB uptake. For in vivo experiments, rats were administered GHB (400-1500 mg/kg) with and without L-lactate. In vitro experiments demonstrated that GHB is transported across the RBC membrane primarily by MCT1 at relevant in vivo concentrations. The K m for MCT1 was lower at pH 6.5 than that at pH 7.4, 2.2 versus 17.0 mM, respectively. The in vivo blood/plasma partitioning of GHB displayed linearity across all concentrations. L-Lactate coadministration increased GHB renal clearance but had no effect on the blood/ plasma ratio. Unlike its MCT-mediated transport in the intestine and kidneys, GHB blood/plasma partitioning appears to be linear and is unaffected by L-lactate. These findings can be attributed, at least in part, to differences in physiologic pH at different sites of MCT-mediated transport.

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“…Transport of L-lactate and pyruvate across the plasma membrane has been studied most extensively in erythrocytes, where a specific monocarboxylate carrier is present (Halestrap, 1976;Deuticke et al, 1978;Dubinsky & Racker, 1978;Deuticke, 1982). At their physiological concentrations, no more than 10 % of total transport occurs by the diffusion of the free acid or on the inorganicanion exchanger, band 3 .…”

Section: Introductionmentioning

confidence: 99%

“…The lactate carrier of erythrocytes catalyses the electroneutral transport of a proton with a monocarboxylate anion (Dubinsky & Racker, 1978; Leeks & Halestrap, 1979). It is stereoselective for L-over D-lactate (Deuticke et al, 1978) and inhibited by a variety of compounds, including a-cyanocinnamate derivatives, organomercurials, amino reagents, quercetin, and high concentrations of the stilbenedisulphonate DIDS (Halestrap & Denton, 1974;Halestrap, 1976;Deuticke et al, 1978;Belt et al, 1979;Jennings & Adams-Lackey, 1982). This carrier has recently been solubilized and functionally reconstituted into lipid vesicles (Poole & Halestrap, 1988).…”

Section: Introductionmentioning

confidence: 99%

The kinetics of transport of lactate and pyruvate into isolated cardiac myocytes from guinea pig. Kinetic evidence for the presence of a carrier distinct from that in erythrocytes and hepatocytes

Poole

Halestrap

Price

et al. 1989

Biochemical Journal

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Stereoselective, SH-dependent transfer of lactate in mammalian erythrocytes

Cited by 117 publications

References 54 publications

Basigin (CD147) Is the Target for Organomercurial Inhibition of Monocarboxylate Transporter Isoforms 1 and 4

Basigin (CD147) Is the Target for Organomercurial Inhibition of Monocarboxylate Transporter Isoforms 1 and 4

γ-Hydroxybutyrate Blood/Plasma Partitioning: Effect of Physiologic pH on Transport by Monocarboxylate Transporters

The kinetics of transport of lactate and pyruvate into isolated cardiac myocytes from guinea pig. Kinetic evidence for the presence of a carrier distinct from that in erythrocytes and hepatocytes

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