RT Journal Article SR Electronic T1 Interaction of fluorescein with the dicarboxylate carrier in rat kidney cortex mitochondria. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1559 OP 1565 VO 279 IS 3 A1 R Masereeuw A1 W C Saleming A1 D S Miller A1 F G Russel YR 1996 UL http://jpet.aspetjournals.org/content/279/3/1559.abstract AB The interaction of the organic anion, fluorescein (FL), with mitochondria in renal proximal tubule cells was investigated. Confocal microscopy was used to demonstrate FL accumulation in mitochondria of intact cells. Phenylsuccinate inhibited the mitochondrial accumulation of the FL analog, carboxyfluorescein (CF) indicating that the dicarboxylate carrier may be involved in the intracellular compartmentation of organic anions. To characterize the interaction, radio-tracer uptake and respiration studies with renal mitochondria were carried out using succinate as a substrate. Respiration measurements in freshly isolated kidney cortex mitochondria revealed that FL inhibited ADP-stimulated and uncoupled respiratory rate, indicating that the organic anion inhibited the availability of succinate as a reducing agent. A similar effect on mitochondrial respiration was found for PAH and phenylsuccinate. FL inhibited 14C-succinate uptake concentration-dependently, and Dixon analysis revealed that the nature of interaction between FL and succinate was competitive, Ki values of 0.5 +/- 0.2 and 1.1 +/- 0.8 mM were calculated for respiration experiments and tracer uptake studies, respectively. The data demonstrate that FL competitively interacts with a mitochondrial dicarboxylate transporter.