The displacement of calcium ions from phospholipid monolayers by pharmacologically active and other organic bases.

1. The binding of (45)Ca(2+) to a monolayer of phosphatidylinositol at the air-water interface was maximal when the separation of the phospholipid head groups approximated to the diameter of a hydrated Ca(2+) ion. 2. The displacement of Ca(2+) adsorbed on monomolecular films of phosphatidylinositol by a series of drugs (both narcotic and excitatory) and other organic bases was related to the ability of the bases to penetrate into the film. 3. With films of phosphatidylinositol at constant area, and at an initial surface pressure of 10dynes/cm., the displacement of Ca(2+) by increasing concentrations of the local anaesthetic, tetracaine, was linearly related to the change in surface pressure (Deltapi) caused by the penetration of the drug. 4. Deltapi and the displacement of Ca(2+) showed a related fall when the initial surface pressure of the phosphatidylinositol film was increased from 4 to 40dynes/cm. both at a constant bulk tetracaine concentration and when this latter concentration was adjusted to keep it at a constant ratio to the surface density of phosphatidylinositol molecules. 5. The displacement of Ca(2+) from phosphatidylinositol films by cetyltri-methylammonium ions was directly compared with the surface concentration of the base in the film, measured by using labelled base and a surface-radioactivity technique. 6. The ability of a series of straight-chain aliphatic amines to displace Ca(2+) from phosphatidylinositol films increased with the number of carbon atoms up to C(12). However, there was a marked jump in the displacing activity after hexylamine, and this could probably be correlated with the carbon chain's being of sufficient length to just reach the hydrophobic fatty acid chains of the orientated phospholipid molecules with the charges on both substances in juxtaposition.