W. O. Berndt

Renal Transport of Diatrizoate in the Rabbit, Dog, and Rat

The renal transport of 125I-diatrizoate was examined in three species, dog, rabbit, and rat. In the rabbit this organic acid behaved like many such compounds, i.e. it was secreted by the pr

Probenecid Binding by Renal Cortical Slices And Homogenates.

Summary The uptake of probenecid by kidney cortex slices was examined over a 100-fold concentration range. This study offers direct evidence implicating tissue binding in the slice uptake process. For example, the steady-state accumulation conformed to a modified “Scatchard plot”. The data were interpreted to mean that two populations of binding sites exist. In addition it was shown that probenecid was bound by kidney cortex homogenates, but not by liver or renal medulla homogenates, an observation in keeping with slice uptake data reported previously.

In vitro accumulation of 14C-xanthine by rabbit renal cortex and its relationship to overall oxypurine transport.

Previous detailed studies of the transport of hypoxanthine and uric acid indicate that these two oxypurines are handled by rather different processes. This report gives information on another importan

Altered mesothelial permeability in the guinea pig following bilateral vagotomy.

Summary The Rb86 and P32-orthophosphate permeability of mesentery removed from vagotomized guinea pigs in terminal stages of pulmonary edema was greater than the permeability of mesentery from control animals. The exposure of guinea pigs to air diluted with nitrogen, producing a sometimes fatal anoxia, did not alter mesothelial permeability or lung weight. Exposure of vagotomized animals to an atmosphere rich in oxygen failed to prevent an increase in mesentery permeability or in lung weight. Vagotomy, however, did not alter the permeability of mesentery taken from reserpine-pretreated animals, although high lung weights indicated pulmonary edema. Because it is improbable that vagotomy affected the permeability only of mesenteric mesothelium, increased permeability of pulmonary membranes may play a role in vagotomy-induced pulmonary edema, whether or not hemodynamic abnormalities are also important. The results with reserpine, however, prove that the mechanism is not identical in lungs and mesentery.

Efflux of Probenecid-14C from Surviving Rabbit Renal Cortex Slices

The runout of ring-labeled probencid 14C from preloaded slices of rabbit kidney cortex has been investigated. Free-hand slices were prepared and permitted to accumulate probenecid from a ba

Inhibition of p-aminohippurate transport by cholegraphic agents.

Summary and Discussion These data show that under proper conditions, and at an appropriate dose, the cholecystography agents can inhibit the transport of PAH both in vitro and in vivo. By inference, this suggests that these agents, or their glucuronide conjugates, may participate in the organic acid transport mechanism of the proximal tubule. This has been demonstrated for iophenoxic acid in a separate study (unpublished observations). Definitive experiments on the other oral agents are not available. In the case of iodipamide, its modest inhibition of PAH secretion in the dog can probably not be attributed to its own participation in proximal transort, since Berndt and Mudge (7) could find no evidence for iodipamide secretion in the dog, although it was demonstrable in the rabbit. Using far larger doses, Lindgren (8) has found marked renal hemodynamic responses to this agent. A major problem posed by these studies is the evaluation of in vivo inhibitory potency. Presumably, either total plasma concentration or the concentration of the free (unbound) drug is the appropriate reference point. Considering iophenoxic acid, for which plasma levels are available, in the first post injection period, at the peak of PAH inhibition, the level of total drug in the plasma was 490 μg/ml, of which 2.9% was free. In the case of probenecid, Beyer et al. (9) found maximal inhibition of PAH secretion at plasma levels of 200 μg/ml. (In the present experiments the dosage of probenecid was probably supramaximal). From the data of Weiner et al. (10), at this plasma level the concentration of free probenecid would be about 60 μg/ml. Even granting the errors intrinsic in the calculation, the data suggest comparable degrees of inhibition of PAH transport at plasma levels of free or unbound drug of 14 μg/ml of iophenoxic acid and 60 μg/ml of probenecid, or, on a molar basis, 2 × 10-5 and 2 × 10-4 M, respectively.