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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.