Effect of Externally Added ATP and Related Compounds on Active Transport of p-Aminohippurate and Metabolism in Cortical Slices of the Rabbit Kidney

Abstract

1. — The uptake of p-aminohippurate (PAH) from oxygenated electrolyte media into thin cortex slices from rabbit kidneys was measured following addition to these media of various nucleotides and related compounds. Furthermore, different metabolic alterations induced by the externally added nucleotides have been investigated. 2. — ATP, ADP, AMP, GTP, UTP, CTP, TTP, 2,3-diphosphoglycerate, and cyclic nucleotide monophosphates inhibited PAH transport by tubular cells to a variable extent, whereas phosphoenolpyruvate, phosphocreatine, and monophosphoglycerates did not significantly affect the accumulation of PAH. No biphasic action of the nucleotides on PAH transport could be detected. 3. — The inhibitory effect of the adenine nucleotides on PAH accumulation was not counteracted by addition of highly oxidizable metabolites like pyruvate and acetate in spite of a complete recovery of renal metabolism, suggesting that the nucleotides interfere directly with the transport of PAH across the tubular cell membrane. 4. — Cyclic nucleotide monophosphates markedly increased the endogenous ATP content in the kidney tissue, particularly in the case of cAMP. Pre-incubation of the cortical slices with cAMP enhanced intracellular ATP level but did not influence the transport of PAH. 5. — Externally added ATP caused an elevation of the concentration of ATP in the tissue accompanied by a reduction of renal glucose degradation and oxygen consumption. On the contrary, ATP promoted the utilization of acetate in the kidney slices. These observations provide evidence for intracellular uptake of ATP. 6. — Moreover, radioactive labelled adenine nucleotides were taken up by the tissue slices through a probenecid-sensitive mechanism. It is suggested that adenine nucleotides are taken up in renal tissue by the common organic anion transport system.