Renal tubular accumulation of organic substances: a new in vivo method which differentiates between luminal and peritubular uptake

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Abstract
Using a modification of the Sperber technique we studied cellular uptake of organic substances in the kidney. A test substance was mixed with an extracellular marker (ethylenediaminetetraacetate or inulin), both radiolabelled with an activity ratio close to 1, and injected into the renal portal system on one side via a leg vein. The animals were killed 1–10 min after injection and the radioactivity in different organs determined. Results showed significantly higher ipsilateral (injection) to contralateral (control) kidney ratios (substance to marker) at 1 min after injection for125I‐Na‐o‐iodohippurate (125I‐Hipp;P< 0.001),14C‐tetraethylammonium bromide (14C‐TEA;P< 0.001),3H‐dihydromorphine (3H‐DHM;P< 0.01), and125I‐iothalamate (P< 0.01), with a progressive decrease in injection kidney ratios for125I‐Hipp and14C‐TEA when death occurred after a longer period. Inhibition of renal tubular transport with novobiocin or mepiperphenidol markedly reduced 1‐ and 4‐min injection kidney ratios for125I‐Hipp and14C‐TEA, respectively. When death occurred after a longer period, ratios in both kidneys increased significantly for125I‐iothalamate. A good correlation was found between peak cellular accumulation in the kidney and excretion efficiency of test substances. Thus, the results indicate (1) that125I‐Hipp,125I‐iothalamate,14C‐TEA, and3H‐DHM were accumulated from the peritubular side of the nephron through the transport systems for organic acids and bases, respectively, and (2) that125I‐iothalamate also showed luminal uptake. In conclusion, this newin vivotechnique is simple and well suited for studying renal tubular accumulation of organic substances and offers the advantage of being able to distinguish luminal from peritubular uptake.