title: myo-Inositol trispyrophosphate: a novel allosteric effector of hemoglobin with high permeation selectivity across the red blood cell plasma membrane.
abstract: myo-Inositol trispyrophosphate (ITPP), a novel membrane-permeant allosteric effector of hemoglobin (Hb), enhances the regulated oxygen release capacity of red blood cells, thus counteracting the effects of hypoxia in diseases such as cancer and cardiovascular ailments. ITPP-induced shifting of the oxygen-hemoglobin equilibrium curve in red blood cells (RBCs) was inhibited by DIDS and NAP-taurine, indicating that band 3 protein, an anion transporter mainly localized on the RBC membrane, allows ITPP entry into RBCs. The maximum intracellular concentration of ITPP, determined by ion chromatography, was 5.5×10(-3) M, whereas a drop in concentration to the limit of detection was observed in NAP-taurine-treated RBCs. The dissociation constant of ITPP binding to RBC ghosts was found to be 1.72×10(-5) M. All data obtained indicate that ITPP uptake is mediated by band 3 protein and is thus highly tissue-selective towards RBCs, a feature of major importance for its potential therapeutic use.
authors.affiliation: Institut de Science et d'Ingénierie Supramoléculaires, Université de Strasbourg, 8 allée Gaspard Monge, 67000 Strasbourg, France.
authors.forename: Carolina D
authors.initials: CD
authors.lastname: Duarte
authors.forename: Ruth
authors.initials: R
authors.lastname: Greferath
authors.forename: Claude
authors.initials: C
authors.lastname: Nicolau
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Lehn
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000494:Allosteric Regulation; D001457:Anion Exchange Protein 1, Erythrocyte / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002463:Cell Membrane Permeability; D004912:Erythrocytes / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007295:Inositol Phosphates / Q000493:pharmacokinetics* / Q000494:pharmacology*; D017136:Ion Transport / Q000187:drug effects; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D006454:Hemoglobins; D007295:Inositol Phosphates; C516441:inositol trispyrophosphate; D013654:Taurine; C010861:NAP taurine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid