title: Organic osmolytes betaine, sorbitol and inositol are potent inhibitors of erythrocyte membrane ATPases.
abstract: Organic osmolytes are used in animal and plant cells to adapt to hyper- and hypoosmolar stress. We used our RBC-membrane model to investigate the effects of the osmolytes betaine, sorbitol and myo-inositol on Na(+)/K(+)-ATPase, Ca(2+)-ATPase and calmodulin-stimulated Ca(2+)-ATPase (CaM). Our results show that betaine inhibited ATPases by more than 61%: Na(+)/K(+)-ATPase (75 +/- 5.9 vs 27 +/- 2.2), Ca(2+)-ATPase (236 +/- 18.9 vs 62 +/- 4.9), and CaM (450 +/- 18 vs 174 +/- 6.9) (microM pi/min/mg protein, control (0 microM betaine) vs 100 micromol/L betaine). Sorbitol (100 micromol/L) inhibited the Ca(2+)-ATPases by 41% (126 +/- 7.6 vs 74 +/- 4.4) and CaM by 42% (253 +/- 17.7 vs 147 +/- 10.3). Inositol (100 micromol/L) inhibited Na(+)/K(+)-ATPase strongest (37 +/- 1.9 vs 20 +/- 1.0; 47% inhibition) while it showed a lesser effect on the Ca(2+)-ATPases (136 +/- 6.8 vs 102 +/- 5.1; 25% inhibition). All osmolytes inhibited RBC membrane ATPases at concentrations above 50 micromol/L, which corresponds to high normal physiologic range for organic osmolytes in serum. Furthermore, the presence of osmolytes (250 micromol/L) decreased hypoosmotic stress induced hemolysis by 42%. Together these data indicate an important regulatory role of organic osmolytes on human RBC membrane ATPases and a protective function of osmolytes in RBCs against hypoosmotic stress.
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, 21st Avenue South, Nashville, TN 37232-2561, USA. gilbert.moeckel@vanderbilt.edu
authors.forename: Gilbert W
authors.initials: GW
authors.lastname: Moeckel
authors.forename: Ramin
authors.initials: R
authors.lastname: Shadman
authors.forename: Joy M
authors.initials: JM
authors.lastname: Fogel
authors.forename: Sayed M H
authors.initials: SM
authors.lastname: Sadrzadeh
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D001622:Betaine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000201:enzymology*; D007294:Inositol / Q000494:pharmacology*; D009994:Osmolar Concentration; D013012:Sorbitol / Q000494:pharmacology*; D014508:Urea / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D001622:Betaine; D007294:Inositol; D013012:Sorbitol; D014508:Urea; D000251:Adenosine Triphosphatases