Organic Base Transport: a Comparative Study

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Abstract
Many studies have been reported in which the renal transport of the organic cations, tetraethylammonium (TEA) and N’-methylnicotinamide (NMN) have been studied. This study was designed to examine the renal handling of these two organic cations by two species, the rat and the rabbit. As reported by others, the renal slice accumulation of NMN by rabbit tissue was poor, with slice/medium (S/M) ratios never exceeding 1. In rat tissue, both cations were accumulated with S/M ratios varying from 4 to 15. Kinetic data support earlier proposals for a dual uptake process for TEA, whereas a single uptake component appeared from NMN in rabbit tissue. NMN uptake by rabbit renal cortex slices was not altered significantly by alterations in bathing solution potassium (0–80 mM), sodium (15–150 mM), or calcium concentrations. TEA uptake in rabbit tissue also was unaffected by alterations in electrolyte concentrations of the bathing solution, with S/M ratios near 10 at all electrolyte concentrations. Significant binding of both cations to renal cortical cytosol was observed. TEA binding to rabbit renal cortical cytosol was reduced with increasing concentrations of TEA. NMN binding to rabbit cytosol increased with increasing cation concentrations in the bathing solution. With rat cytosol, both cations were bound from 6 to 10%, and the binding was unaffected by alterations in cation concentrations. In subcellular fractionation studies in both species, TEA showed a higher binding in the initial low-speed fraction and a lower binding in the final supernatant than did NMN. The extent of TEA binding in the low-speed fractions was reduced significantly by incubation of the homogenates with 10-3Af 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). 2,4,5-T had no effect on the subcellular distribution of NMN in either rat or rabbit tissue. Unidirectional runout studies indicated that NMN efflux from preloaded rabbit renal cortex slices was faster than that for TEA. The NMN runout rate constants were similar to those reported earlier for rat tissue. The relatively slow efflux of TEA from rabbit renal cortical tissue was unaffected by phenoxybenzamine, cyanine No. 863, NMN, or alterations in bathing solution potassium concentration. On the other hand, effects on NMN efflux were observed.