Phospholipid dynamics and function in cell membrane of blood cells. With reference to mode of action of certain amphiphilic drugs

An asymmetric modification of the cell membrane lipid bilayer of erythrocytes by means of exogenous phospholipase (PL) treatment or of phospholipid addition induced an echinocyte- or stomatocyte-type shape change of the cells. Such membrane shape change was demonstrated to be due to asymmetric swelling or shrinkage of the lipid bilayer halves, from the simultaneous determination of the change or intra-bilayer transfer of the phospholipid molecules. In the collagen-induced activation of blood platelets, the importance of PLA2 activation as the initial reaction of the signaling system was demonstrated, and the regulatory effects of the membrane fluidity change on the enzyme activation were also shown. In the antigen-induced activation of peritoneal mast cells, a pathway through the PLD activation appeared to be more important. Phosphatidic acid produced from the membrane phospholipids through the PLD activation was shown to act as an intracellular mediator to stimulate the PLA2 activation. Various amphiphilic drugs, including benzylisoquinoline alkaloids such as cepharanthine, were shown to inhibit the platelet activation and the mechanism was studied. The anti-platelet activity appeared to be mainly due to inhibition of the PLA2 activation.