Abstract
NCO-650 exerted a dose-dependent inhibition of histamine release from isolated rat mast cells without affecting the Ca-uptake and intracellular cAMP levels. When the membrane stabilizing action of NCO-650 was investigated with the liposomes prepared by various phospholipids with or without cholesterol, it became clear that compound 48/80 decreases the order parameter of liposomes and NCO-650 inhibits the decrease of order parameter. Histamine release from histamine-containing liposomes was brought about by compound 48/80 at concentrations higher than 0.5 micrograms/ml, and pretreatment of the liposomes with NCO-650 inhibited histamine release due to compound 48/80. The incorporation of NCO-650 in the liposomes was effective in abolishing the phase transition of the lipid bilayer membranes from crystalline gel to liquid crystalline phases, and decreased the phase transition temperature. Those changes in the lipid bilayer membranes correspond to those displayed by incorporation of cholesterol in the liposomes. An increase of permeability of lipid membrane by compound 48/80 may be due to partial loosening of the lipid order; NCO-650 rigidified the liposome membrane and as a result of this, it decreased histamine release.
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