Biological activities of metal ion-binding compounds can be changed in the response to the increment of the metal concentration, and based on the latter compounds can be classified as "metal ionophores", "metal chelators" or "metal shuttles". If the biological effect is augmented by increasing the metal concentration, it is classified as a "metal ionophore". If the biological effect is decreased or reversed by increasing the metal concentration, it is classified as a "metal chelator". If the biological effect is not affected by increasing the metal concentration, and the compound-metal complex enters the cell, it is classified as a "metal shuttle". The term ionophore (from Greek "ion carrier" or "ion bearer") was proposed by Berton Pressman in 1967 when he and his colleagues were investigating the antibiotic mechanisms of valinomycin and nigericin.