THE BIOCHEMORPHOLOGY OF RENAL TUBULAR TRANSPORT: IODINATED BENZOIC ACIDS

¹ Department of Pharmacology, School of Medicine, University of Louisville, Louisville, Kentucky

Benzoic acid and fourteen iodinated derivatives with hydroxyl, amino, and acylamido substituents have been studied for solubility, acidity, binding by plasma proteins, lethal toxicity, uptake by slices of renal cortex, and disposal by the dog kidney in situ.

Lethal toxicity appears better to correlate directly with protein binding than inversely with solubility or with acidity. Substitution in benzoic acid of iodine alone or iodine and hydroxyl or amino groups increases toxicity. Acylamido substitution confers low toxicity. Lowest toxicity is present when all positions on the ring are occupied.

Renal cortical slices take up all the compounds so that the concentration in the slice ranges from three to twenty-one times that in the medium. The ratio of concentration in the slice to that in the medium is reduced by Benemid in only ten of the compounds and not greatly so in these. With seven of the compounds this ratio is higher in slices coagulated by heat than in normal slices. Comparison of uptake with extent of binding by plasma protein indicates a positive correlation, suggesting that uptake of many of these compounds may be a phenomenon of protein binding rather than one of cellular transport.

In the kidney in situ, benzoic acid and ten of its derivatives are reabsorbed from glomerular filtrate by the tubules. Three of the derivatives which are reabsorbed to a smaller extent than are the others have greatly different solubility and acidity but show comparatively low degree of protein binding. However, benzoic acid is extensively reabsorbed and shows no protein binding.

Four of the compounds are excreted by the renal tubules; these compounds have an acylamido group in the 3, the 4, or 3,5 position. An acylamido group in the 2 position does not lead to tubular excretion.

Three of these four compounds exhibit a maximal rate of tubular excretion, apparently being transported by the same mechanism, with the transport from cell to lumen being the limiting reaction. The fourth compound exhibited no maximal rate of transport, this apparently being limited by the rate of entrance into the cell.

X-ray visualization of the urinary system was achieved only by compounds that are excreted by the tubules.