Erythrocyte shape and volume changes caused by an inhibitor of the glucose and anion transporters.
Light scattering measurements and scanning electron microscopy show that p-azidobenzylphlorizin (p-AzBPhz) causes changes in the shape and volume of human erythrocytes by at least two, dose-dependent mechanisms: At nominal concentrations above 5 microM, the azide induces cell swelling by either enlarging a pre-existent channel or by creating pores between phase boundaries of the membrane through which salt and water enter, but sucrose remains excluded. However, over the range 0.03 to 0.3 microM, in either isosmotic NaCl or KCl media, when fewer than 1 million molecules of azide are bound per cell, the ligand causes membrane deformations that convert discocytes into cells resembling stage 2 echinocytes. Whereas a cell volume increase of about 10% accompanies these shape changes, (microhematocrit and electronic cell sizing measurements), no net influx of either Na+ or K+ during this stage of swelling was detectable. These cell alterations take place at p-AzBPhz concentrations which concurrently inhibit both chloride and 3-methoxyglucose equilibrium exchange transport. The results may indicate that when the membrane impermeable p-AzBPhz interacts with the anion and/or sugar transporter, some trans-membrane perturbation occurs which alters the cytoskeleton.
Blank
M E
ME
Department of Pharmacology, University of Kentucky, Lexington 40536.
Diedrich
D F
DF
D001386:Azides / Q000737:chemistry / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004911:Erythrocyte Volume / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D008027:Light; D008855:Microscopy, Electron, Scanning; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors*; D010695:Phlorhizin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D012542:Scattering, Radiation; D013053:Spectrophotometry
D001386:Azides; D009004:Monosaccharide Transport Proteins; C056185:phlorizinyl 5'-benzylazide; D010695:Phlorhizin