Ionophorous properties of neutral diamide ligands toward calcium.

The ability of a series of aromatic and alicyclic analogues of 1,2-ethylenedioxydiacetic acids bearing N,N,N',N'-tetra-n-propyl amide or N-methyl-N-carbethoxypentyl amide linkages to enhance the rate of 45Ca2+ efflux from vesicles was studied. The ligands were less potent in enhancing membrane permeability to Ca2+ than A23187 and X537A. Lipid-soluble anions markedly increased the rate and extent of Ca2+ transport mediated by these neutral ligands. The abilities of these synthetic diamide ligands and naturally occurring ionophores to transport Ca2+ across bilayer membranes were sensitive to the lipid composition of the vesicle. The mechanism of Ca2+ transport mediated by this series of synthetic ligands is discussed.