N,N'-dicyclohexylcarbodiimide inactivates organic cation transport in renal brush border membranes.


The molecular mechanism of the electroneutral organic cation/H+ antiporter in renal brush border membrane vesicles was studied utilizing the prototypic organic cation N1-methylnicotinamide. The hydrophobic carbodiimide, N,N'-dicyclohexylcarbodiimide (DCCD), inactivated organic cation transport irreversibly with an IC50 of 2.6 microM at pH 7.5 and 40 nM at pH 6.0. On the other hand, the hydrophilic reagents, 1-ethyl-3-[3-(dimethylamino)-propyl]carbodiimide and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, did not affect organic cation transport. Substrate did not affect the rate of the DCCD inactivation which followed pseudo-first-order-kinetics. A double logarithmic plot of the apparent rate constants vs. the DCCD concentration gave a straight line with a slope of 0.8. The data are consistent with a simple bimolecular reaction mechanism and imply that one molecule of DCCD inactivates one carboxylate group per active transport unit and that the carboxylate group is critical for transport.

Cite this paper

@article{Sokol1987NNdicyclohexylcarbodiimideIO, title={N,N'-dicyclohexylcarbodiimide inactivates organic cation transport in renal brush border membranes.}, author={P P Sokol and Peter D Holohan and C. R. Ross}, journal={The Journal of pharmacology and experimental therapeutics}, year={1987}, volume={243 2}, pages={455-9} }