Effect of phospholipase A2 and cholesterol oxidase on perazine and promethazine penetration into human erythrocytes and on fluidity of the membrane.

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Abstract
To clarify the mode of action of drugs on human erythrocyte membrane and the role of lipids in transmembrane transport of drugs, the cell and membrane were treated with phospholipase A2 and cholesterol oxidase respectively, and the penetration of perazine and promethazine into the membrane and the membrane fluidity were estimated. It was found that 58.3% of phosphatidylcholine in the membrane was hydrolyzed. The fluidity of the membrane, estimated by the electorn spin resonance method, was significantly enhanced by phospholipase A2 treatment. When lysophosphatidylcholine and fatty acids produced were extracted by using albumin, the fluidity was greatly decreased. Although the treatment with cholesterol oxidase induced degradation of 24% of the cholesterol in the membrane, the fluidity was not altered. The amounts of these drugs that penetrated into the erythrocytes were significantly increased after phospholipase A2 treatment, but dramatically decreased after the extraction of the products formed by phospholipase A2, while the amounts were not significantly increased by cholesterol oxidase treatment. These results led us to postulate that phospholipids in the erythrocyte membrane are probably involved in the penetration of the two drugs, whereas the involvement of cholesterol is far less, and that the increased fluidity of the membrane lipids certainly contributes to the enhancement of penetration.