Inhibition of beta-amino acid transport by diamide does not involve the brush border membrane surface.
Diamide (dicarboxylic acid bis-(N,N-dimethylamide) has been shown in previous studies to block the uptake of the beta-amino acid taurine at its high affinity transport site in rat renal cortex slices. Diamide may act by increasing the efflux of taurine from the slice. Studies performed in rat slices again indicate enhanced efflux over 8-12 minutes. The time course of reduced glutathione (GSH) depletion from renal cortex is similar, indicating a potential interaction between GSH depletion and inhibition of taurine accumulation. Diamide further blocks the uptake of taurine by collagenase-isolated renal tubules in a dose-dependent fashion with greater inhibition at 20 minutes than at 5 minutes. The effect of 9 mM diamide on the Na+ -dependent accumulation of taurine (10 and 250 microM) by brush border membrane vesicles was examined, and the taurine uptake value both initially and at equilibrium was the same in the presence and absence of diamide. That the effect in tubules is greater at 20 minutes than at 5 minutes is consistent with the idea that diamide enhances efflux of taurine immediately after exposure of tubules to taurine, or that diamide influences some intracellular process, requiring a time interval before this action is observed. Isolation of the brush border surface and subsequent transport studies of taurine are not influenced by diamide. Thus, diamide inhibition of taurine uptake does not involve physiochemical alteration of the membrane surface where active amino acid transport occurs, despite the thiol-oxidizing properties of this agent. Further, these studies suggest that diamide either acts at the basolateral surface, rather than the brush border surface of rat renal cortex or requires the presence of an intact tubule, capable of metabolism, prior to its inhibitory action.
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D003958:Diamide / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013654:Taurine / Q000378:metabolism*
D001391:Azo Compounds; D002250:Carbon Radioisotopes; D003958:Diamide; D013654:Taurine; D005978:Glutathione