Molecular features of organic anion permeablity in ox red blood cell.

1. The penetration of organic anions into bovine red blood cells has been studied under experimental conditions where it could be distinguished from the penetration of undissociated acids which proceeds by diffusion through lipid zones of the membrane. 2. Several lines of evidence suggest that the entry of organic anions cannot be ascribed to simple diffusion across aqueous channels limited by positive charges but needs a specific interaction of the penetrating anion with a component of the membrane. 3. The structural requirements allowing for ionic transfer is a strong polar head for the smallest molecules and in addition an amphiphilic structure for acids with chain length greater than C4. Interaction between substrate and receptor requires at least a three point attachment involving three oxygen atoms in the substrate which react with complementary loci on the receptor to form ionic and hydrogen bonds. Such a three point attachment can be made by a sulphonic group or with carboxylic acid by alpha ketosubstitution, alpha hydroxysubstitution, addition of an amidegroup or addition of a second carboxyl group spatially close to the first. 4. As suggested by the behaviour of the formate anion, in such a transport system any carboxylic acid could interact transiently with the receptor and therefore interfere with the transport of an organic anion even though such ionic interaction with the receptor were insufficient to produce transport of the acid itself.