Suramin: A potent ATPase inhibitor which acts on the inside surface of the sodium pump

1. (1) The impermeant polyanion suramin inhibits the (Na+ - K+)-activated ATPase in broken membrane preparations. Suramin does not affect Na+ or K+ transport in intact red cells or resealed red cell ghosts when present in the incubation medium, but appears to inhibit the Na+ pump in ghosts resealed with suramin inside. Other ATP-requiring enzymes are also inhibited by suramin with similar potency (50% inhibition at 10−5-10−4 M) suggesting an interaction with the substrate site of the enzyme. 2. (2) K+-activated p-nitrophenylphosphatase activity and [3H]ouabain binding are also inhibited by suramin. 3. (3) The inhibition by suramin is reversed by washing the membranes. 4. (4) It is concluded that suramin inhibits the Na+-K+ transport system through interactions with the intracellular part of the pump. 5. (5) The potential usefulness of suramin as a pump inhibitor and the possibility of modifying its structure to yield fluorescent derivatives are discussed.