Renal tubular accumulation of organic substances: a new in vivo method which differentiates between luminal and peritubular uptake.
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 I, 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 for 125I-Na-o-iodohippurate (125I-Hipp; P less than 0.001), 14C-tetraethylammonium bromide (14C-TEA; P less than 0.001), 3H-dihydromorphine (3H-DHM; P less than 0.01), and 125I-iothalamate (P less than 0.01), with a progressive decrease in injection kidney ratios for 125I-Hipp and 14C-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 for 125I-Hipp and 14C-TEA, respectively. When death occurred after a longer period, ratios in both kidneys increased significantly for 125I-iothalamate. A good correlation was found between peak cellular accumulation in the kidney and excretion efficiency of test substances. Thus, the results indicate that 125I-Hipp, 125I-iothalamate, 14C-TEA, and 3H-DHM were accumulated from the peritubular side of the nephron through the transport systems for organic acids and bases, respectively, and that 125I-iothalamate also showed luminal uptake. In conclusion, this new in vivo technique 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.
D000818:Animals; D001693:Biological Transport, Active; D002250:Carbon Radioisotopes; D002645:Chickens; D002860:Chromium Radioisotopes; D004090:Dihydromorphine; D004492:Edetic Acid; D005260:Female; D007444:Inulin; D007457:Iodine Radioisotopes; D007458:Iodipamide; D007465:Iodohippuric Acid; D007483:Iothalamic Acid; D007684:Kidney Tubules / Q000378:metabolism*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds; D014316:Tritium
D002250:Carbon Radioisotopes; D002860:Chromium Radioisotopes; D007457:Iodine Radioisotopes; D013757:Tetraethylammonium Compounds; D014316:Tritium; D007465:Iodohippuric Acid; D007483:Iothalamic Acid; D019789:Tetraethylammonium; D007444:Inulin; D004492:Edetic Acid; D004090:Dihydromorphine; D007458:Iodipamide