K. J. Ullrich

Phenomenologic description of Na+, Cl− and HCO 3 − absorption from proximal tubules of the rat kidney

SummaryProximal tubules of the rat kidney were perfused in vivo with NaCl-NaHCO3 Ringers solution and the net rates of fluid absorption from Gertz shrinking drops were measured as well as the stationary electro-chemical potential differences for Na+ and Cl− that develop across the tubular wall during constant fluid absorption. By altering the rate of fluid absorption through addition of raffinose to the peritubular perfusate or to the lumen fluid, the relations between the net ion fluxes and the electrochemical potential differences were obtained for Na+, Cl− and HCO3−. From these relations which were reasonably linear for Na+ and Cl− over small deviations from equilibrium, single ion reflection coefficients and active transport rates were calculated. Since the calculations required a knowledge of the permeability coefficients of the tubular wall for Na+ and Cl−, in a separate series of experiments these coefficients were determined from tracer flux experiments. The calculations yield σNa=0.7, and σCl=0.5

The role of bicarbonate and other buffers on isotonic fluid absorption in the proximal convolution of the rat kidney.

\sigma _{HCO_2 }

Active Ca2+ reabsorption in the proximal tubule of the rat kidney

can be estimated to be substantially greater than σCl. Comparing the active transport rates to the net fluid absorption under conditions similar to free flow in the normal kidney, the following conclusions can be drawn: approximately one third of the sodium is resorbed by active transport, one third by electrical transference and one third by solvent drag. Chloride transport is entirely passive. One half of the chloride is resorbed by diffusion and one half by solvent drag. Bicarbonate transport appears to be entirely active, and the active transport rate is greater than the net transport pointing to passive bicarbonate back flux.

Specificity and sodium dependence of the active sugar tansport in the proximal convolution of the rat kidney

Recently multisubstrate specificity became popular through studies of multidrug resistance in tumor cells [16] and bacteria [43]. The phenomenon of multisubstrate specificity, however, was recognized long ago in studies of the transport of organic anions and organic cations in the kidney [11, 21, 48, 83] and the liver [36]. Actually all xenobiotics (chemicals and drugs), which are taken up by animals are finally excreted by these organs, either directly or after metabolic transformation. Thereby only few transporters are involved. The questions discussed in this review are: (i) what renal transporters participate in the transport of these substances which can be subsumed under organic anions and organic cations? (ii) What are the molecular features of substrates which are recognized by the respective transporters? In Fig. 1 the main transport systems for organic anions and organic cations on either cell side of the proximal renal tubule are depicted. Anion transporters: 1. The contraluminal para-aminohippurate (PAH)/ aketoglutarate exchange system, the main transport system for the secretion of organic anions, not potential sensitive, cloned, sequence not yet published [38, 84]. 2. The luminal anion/anion exchange system(s); for x −

Coupling between proximal tubular transport processes

SummaryThe fluid reabsorption from the proximal convolution of the rat kidney was measured with the Gertz shrinking droplet technique. Simultaneously, the peritubular capillaries were perfused with artificial solutions. In some experimental series, fluid from the shrinking droplet was withdrawn and analysed for Cl−, Na+, and osmolality so that the transtubular transport of Na+, Cl−, and HCO3− could be calculated. Capillary perfusate in some experiments was also withdrawn and its pH was measured. The following results were obtained: 1. With increasing concentration of HCO3− in the capillary perfusate, the transtubular water, sodium, chloride, and bicarbonate reabsorption increased. 2. The sulfonamide buffers sulfamerazine and glycodiazine (Redul®), which easily penetrate the tubular wall, could, in equimolar concentrations, substitute totally for the bicarbonate buffer in promoting isotonic fluid absorption. 3. Butyrate, propionate, and acetate were also effective; pyruvate, lactate, and paraaminohippurate, however, were not. 4. The effect of HCO3− and glycodiazine on isotonic absorption was shown to depend exclusively on the concentration of the buffer anion and not on the concentration of undissociated acid or pH. From these data it is suggested that for proximal isotonic absorption of water, sodium, and chloride, the reabsorption of buffer anions via H+ secretion and nonionic diffusion may be essential. The H+ secretion or the buffer anion absorption across the luminal cell wall may secondarily influence the active Na+ transporting mechanism located at the basal cell site either by a luminal H+−Na+ exchange mechanism or by a lyotropic effect which would increase the Na+ permeability of the luminal cell site. Thereby more Na+ would be delivered to the Na+ pumping site and the rate of Na+ pumping would be augmented.

Secretion and contraluminal uptake of dicarboxylic acids in the proximal convolution of rat kidney

SummaryWith the technique of stop flow microperfusion with simultaneous capillary microperfusion the zero net flux transtubular concentration differences (Δc) of labelled amino acids which are equivalent to their active transport rates were measured. Alll-amino acids tested (phenylalanine, histidine, aminobicycloheptane-carboxylic acid, aminoisobutyric acid; lysine, ornithine, arginine; aspartic acid; proline and glycine) showed a considerable Δc, i.e. active transport rate. When, however, the ambient sodium was replaced by choline the Δc values dropped to zero. An analysis of the Na+ dependence of the ornithine transport revealed that the sodium-dependence is of the mixed type, i.e. thatKmdecreased andVmax increased with increasing Na+ concentration to the same extent.In contrast to other biological systems no mutual interaction between the Na+-dependentd-glucose andl-histidine transport could be observed.Incidental to these studies it was observed that the active transport rate ofd-histidine was in the range of 40% of that of thel-isomer while ford-phenylalanine it was only in the range of 10% of the active transport of thel-isomer. Furthermore it was found that thel-aspartic acid transport was already saturated at a luminall-aspartic acid concentration of 0.05 mmol/l while that ofl-phenylalanine was not saturated even at a luminal concentration of 9 mmol/l.

Renal phosphate transport: inhomogeneity of local proximal transport rates and sodium dependence.

SummaryUsing the stop flow microperfusion technique with simultaneous capillary perfusion the rate of active Ca2+ reabsorption was evaluated by measuring the static head electrochemical potential difference as well as the permeability of the tubular wall for Ca2+ ions. Under control conditions the active Ca2+ transport was calculated to be 3.35×10−13 mol/cm·s. It declined toward zero if the ambient Na+ was replaced by choline or lithium. Parallel experiments in the golden hamster showed that active Ca2+ transport, vanished completely if active Na+ transport was blocked by ouabain (1 mM). These data indicate that the active Ca2+ reabsorption from the proximal tubule depends on the active reabsorption of Na2+ presumably via a Na+−Ca2+ countertransport at the contraluminal cell membrane. The static head electrochemical potential difference of Ca2+ is the same in late and early proximal tubules. It is also not affected by the presence of acetazolamide (10−4 M) by the absence of bicarbonate or glycodiazine buffer or by the absence or presence of phosphate (2 mM).

Bisubstrates: substances that interact with both, renal contraluminal organic anion and organic cation transport systems

SummaryWith the technique of stop flow microperfusion with simultaneous capillary perfusion, the zero net flux transtubular concentration difference (Δc) of labelled sugars was measured.The following sequence of Δc values, which are a measure for the active transtubular transport rate, were evaluated:d-glucose ≅β methyl-d-glycoside >α-methyl-d-glycoside >d-galactose >3-O-methyl-glucose >d-allose. When 10−4 M phlorrhizin was given in the luminal perfusate the Δcs dropped to zero (±8%). Δc-values in the same range i.e. indicating no active transport, were found for:l-glucose,d-mannose, 2-deoxy-d-glucose,d-fructose,d-glucosamine, 6-deoxy-d-galactose (=d-fucose),d-ribose and the reference polyalcohold-mannitol. Inhibition of thed-galactose δc was achieved by 15 mmol/l of the following sugars: α-methyl-d-glycoside ≅d-glucose ≅ 6-deoxy-d-glucose >3-O-methyl-d-glucose an no significant inhibition byd-xylose andd-mannose. Against Δc of α-methyl-d-glucose the following inhibitory potency was observed:d-glucose >6-deoxy-d-glucose >3-O-methyl-d-glucose ≅d-galactose >d-xylose and no inhibition byd-mannose.When the ambient sodium was replaced by choline, the Δc values of all actively transported sugars dropped toward zero. An analysis of the Na+ dependence of the α-methyl-d-glycoside transport revealed that the sodium dependence is of the affinity type i.e. that onlyKmincreased with increasing Na+ concentration whileVmax remained almost constant.From these data one can conclude: 1. The Crane specificity, i.e. that only the α-position of the OH-group on carbon atom 2 is essential, which was found for the intestinal hexose transport holds for the rat proximal kidney tubule, too. 2. The hexose transport system in the rat works only when Na+-ions are present. The sodium ions augment the affinity of the hexose transport system for the hexoses.