Membrane action of phlorizinyl 5'-benzylazide induces volume and shape change of human erythrocytes and sickle cells.
In the absence of light, phlorizinyl benzylazide is a potent competitive inhibitor of sugar transport (app. Ki about 1.5 uM) and a reversible inhibitor of chloride exchange (app. Ki about 2 uM) in the normal red cell. It causes additional membrane alterations at about 10-fold higher concentrations which lead to a time-, pH-, temperature-, and cell storage time-dependent increase in cell volume in isosmotic phosphate-buffered saline. This drug effect may be related to its interaction with Bands 3 and 4.5 (both become covalently labeled when the azide is light activated) such that cation conductance is increased. Apparently, a channel is created or widened through which salt and water (but not sucrose) can enter causing cell swelling and eventually lysis. The membrane probe is capable of inhibiting deoxygenation-induced sickling of SS and SC cells; under conditions that cause normal cell bursting, sickle cells swell but do not lyse.
Maynard
C L
CL
Department of Pharmacology, University of Kentucky, Lexington 40536.
Diedrich
D F
DF
D000255:Adenosine Triphosphate / Q000097:blood; D000755:Anemia, Sickle Cell / Q000097:blood*; D001386:Azides / Q000494:pharmacology; D002021:Buffers; D003080:Cold Temperature; D004734:Energy Metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects* / Q000473:pathology; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010042:Ouabain / Q000494:pharmacology; D010695:Phlorhizin / Q000031:analogs & derivatives / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood; D013053:Spectrophotometry; D013997:Time Factors
D001386:Azides; D002021:Buffers; C056185:phlorizinyl 5'-benzylazide; D010042:Ouabain; D000255:Adenosine Triphosphate; D010695:Phlorhizin; D000254:Sodium-Potassium-Exchanging ATPase