Membrane transport of nucleobases: interaction with inhibitors.

1. The kinetic properties and the mechanism of nucleobase transport and transport inhibition are briefly reviewed. 2. Many purine derivatives even when bearing large substituents on N9 and C6 are inhibitors of nucleobase transport, some are also substrates. 3. Papaverine and other benzyl-isoquinolines are efficient inhibitors of facilitated transport of nucleobases. 4. Papaverine is a noncompetitive inhibitor of nucleobase transport in human erythrocytes. 5. Reduction of the aromatic isoquinoline to the tetrahydro form causes loss of inhibitory activity whereas replacement of methoxy groups by ethoxy groups leads to increased activity. 6. Papaverine also inhibits sodium dependent active nucleobase transport in pig kidney cells. 7. The nucleoside transport inhibitors dipyridamole and dilazep have no effect on facilitated diffusion transport of nucleobases, but inhibit in micromolar concentrations active sodium dependent nucleobase transport in pig kidney cells.