Stilbenedisulfonate Binding Kinetics to Band 3 (AE 1): Relationship between Transport and Stilbenedisulfonate Binding Sites and Role of Subunit Interactions in Transport

Salhany, James M.

doi:10.1006/bcmd.2000.0369

Cited by 13 publications

(10 citation statements)

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“…A lack of influence of DIDS on nitrite permeation was also reported in carp (Jensen 1990) and human (May et al 2000) erythrocytes. DIDS may bind to a different site than the AE1 transport site (Salhany 2001), so one may envisage a different potency of DIDS among species (because of different AE1 primary structure), as has also been observed (Jensen & Brahm 1995). DIDS may bind to a different site than the AE1 transport site (Salhany 2001), so one may envisage a different potency of DIDS among species (because of different AE1 primary structure), as has also been observed (Jensen & Brahm 1995).…”

Section: Mechanism Of Nitrite Permeation Of the Membranementioning

confidence: 81%

“…Contrasting with this is a report of inhibition of HCO 3 ) /NO 2 ) exchange by DIDS in horse RBC ghosts (Shingles et al 1997). DIDS may bind to a different site than the AE1 transport site (Salhany 2001), so one may envisage a different potency of DIDS among species (because of different AE1 primary structure), as has also been observed (Jensen & Brahm 1995). The accumulating trend of an absent influence of DIDS on nitrite transport in intact RBCs, however, seems to argue against an involvement of AE1.…”

Section: Mechanism Of Nitrite Permeation Of the Membranementioning

confidence: 81%

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Nitrite transport into pig erythrocytes and its potential biological role

Frank

2005

Acta Physiologica Scandinavica

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Section: Mechanism Of Nitrite Permeation Of the Membranementioning

confidence: 81%

Section: Mechanism Of Nitrite Permeation Of the Membranementioning

confidence: 81%

Nitrite transport into pig erythrocytes and its potential biological role

Frank

2005

Acta Physiologica Scandinavica

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“…However, two stilbene-reactive lysines in AE1 appear to have allosteric effects on substrate binding (31). More recently, Salhany (35) has presented kinetic evidence that stilbenes compete allosterically rather than directly with substrate binding. Although the stilbene and substrate binding sites appear to be distinct, stilbene binding may interfere with accessibility of the translocation pathway.…”

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confidence: 99%

A Cysteine-scanning Mutagenesis Study of Transmembrane Domain 8 of the Electrogenic Sodium/Bicarbonate Cotransporter NBCe1

McAlear

Bevensee

2006

Journal of Biological Chemistry

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, and the corresponding domain in NBCe1 variants is highly homologous. We performed cysteine-scanning mutagenesis to examine the role of TMD8 residues in ion translocation by rat NBCe1-A. We accessed function and/or sulfhydryl sensitivity and p-chloromercuribenzene sulfonate ( pCMBS) accessibility of 21 cysteinesubstituted NBC mutants expressed in Xenopus oocytes using the two-electrode, voltage clamp technique. Five NBC mutants displayed <10% wild-type activity: P743C, A744C, L746C, D754C, and T758C. For the remaining 16 mutants, we compared transporter-mediated inward currents elicited by removing external Na ؉ before and after exposing oocytes to either 2-aminoethylmethane thiosulfonate (MTSEA) or pCMBS. MTSEA inhibited NBC mutants T748C, I749C, I751C, F752C, M753C, and Q756C by 9 -19% and stimulated mutants A739C, A741C, L745C, V747C, Q755C, and I757C by 11-21%. pCMBS mildly inhibited mutants A739C, A740, V747C, and Q756C by 5 or 8%, and stimulated I749C by 10%. However, both sulfhydryl reagents strongly inhibited the L750C mutant by >85%. Using the substituted cysteine accessibility method, we examined the accessibility of the NBC mutant L750C under different transporter conditions. pCMBS accessibility is (i) reduced when the transporter is active in the presence of both Na ؉ and HCO 3 ؊ , likely due to substrate competition with pCMBS; (ii) reduced in the presence of a stilbene inhibitor; and (iii) stimulated at more positive membrane potentials. In summary, TMD8 residues of NBCe1, particularly L750, are involved in ion translocation, and accessibility is influenced by the state of transporter activity.Sodium/bicarbonate cotransporters (NBCs) 2 are proteins that cotransport HCO 3 Ϫ and/or CO 3 2Ϫ with Na ϩ across plasma membranes, thereby contributing to the regulation of intracellular pH (pH i ) and ion homeostasis in many tissues, including kidney, heart, and brain. Electrogenic NBCs, including NBCe1 and NBCe2, as well as electroneutral NBCs such as NBCn1 have been cloned, characterized, and localized in many tissues and cell types (1, 2). Splice variants exist for the different NBCs. For example, NBCe1 contains three splice variants that differ at their amino and/or carboxyl termini: NBCe1-A, -B, and -C. Based on sequence homology, NBCs in conjunction with anion exchangers (AEs) and sodium-driven chloride-bicarbonate exchangers are members of a superfamily of bicarbonate transporters.Over the last several years, considerable molecular advances have been made in understanding both the function and regulation of cloned NBCs, particularly NBCe1 variants. When expressed in Xenopus oocytes, all three NBCe1 variants have similar ion and voltage dependences, although the A variant is ϳ4-fold more active than the B and C variants due to its unique amino terminus (3). However, functional properties of the transporters (e.g. stoichiometry) appear to be cell-type-dependent (4). NBC activity was first characterized in the salamander proximal tubule (5), and the cDNA encoding the protein was later cloned by Romero e...

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“…While an absent influence of DIDS on nitrite uptake in carp (20), human (31), and pig (21) RBCs seems to argue against the involvement of AE1, the finding of DIDS inhibition of NO 2 Ϫ /HCO 3 Ϫ exchange in horse RBC ghosts (41) favors the AE1 route. In light of the fact that DIDS binds to a different site than the AE1 transport site (38) and has a different potency among species (26), an AE1 knockout model would seem ideal for evaluating the role of AE1 in RBC nitrite transport. Hagfish and lampreys are special among all chordates/vertebrates by being functionally devoid of AE1 in their RBCs (6,11,34,35,43), and they thus provide natural knockout models for such an investigation.…”

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confidence: 99%

Comparative analysis of nitrite uptake and hemoglobin-nitrite reactions in erythrocytes: sorting out uptake mechanisms and oxygenation dependencies

Frank

Rohde

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Nitrite uptake into red blood cells (RBCs) precedes its intracellular reactions with hemoglobin (Hb) that forms nitric oxide (NO) during hypoxia. We investigated the uptake of nitrite and its reactions with Hb at different oxygen saturations (So(2)), using RBCs with (carp and rabbit) and without (hagfish and lamprey) anion exchanger-1 (AE1) in the membrane, with the aim to unravel the mechanisms and oxygenation dependencies of nitrite transport. Added nitrite rapidly diffused into the RBCs until equilibrium. The distribution ratio of nitrite across the membrane agreed with that expected from HNO(2) diffusion and AE1-mediated facilitated NO(2)(-) diffusion. Participation of HNO(2) diffusion was emphasized by rapid transmembrane nitrite equilibration also in the natural AE1 knockouts. Following the equilibration, nitrite was consumed by reacting with Hb, which created a continued inward diffusion controlled by intracellular reaction rates. Changes in nitrite uptake with So(2), pH, or species were accordingly explained by corresponding changes in reaction rates. In carp, nitrite uptake rates increased linearly with decreasing So(2) over the entire So(2) range. In rabbit, nitrite uptake rates were highest at intermediate So(2), producing a bell-shaped relationship with So(2). Nitrite consumption increased approximately 10-fold with a 1 unit decrease in pH, as expected from the involvement of protons in the reactions with Hb. The reaction of nitrite with deoxyhemoglobin was favored over that with oxyhemoglobin at intermediate So(2). We propose a model for RBC nitrite uptake that involves both HNO(2) diffusion and AE1-mediated transport and that explains both the present and previous (sometimes puzzling) results.

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Stilbenedisulfonate Binding Kinetics to Band 3 (AE 1): Relationship between Transport and Stilbenedisulfonate Binding Sites and Role of Subunit Interactions in Transport

Cited by 13 publications

References 25 publications

Nitrite transport into pig erythrocytes and its potential biological role

Nitrite transport into pig erythrocytes and its potential biological role

A Cysteine-scanning Mutagenesis Study of Transmembrane Domain 8 of the Electrogenic Sodium/Bicarbonate Cotransporter NBCe1

Comparative analysis of nitrite uptake and hemoglobin-nitrite reactions in erythrocytes: sorting out uptake mechanisms and oxygenation dependencies

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