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Abstract

The kinetics ofl-histidine reabsorption by the proximal convolution of the rat nephron have been studied by stationary microperfusion with simultaneous perfusion of peritubular capillaries. Steady-state concentrations (C_∞) and transepithelial concentration differences (Δc_∞) were determined over a wide range of peritubular bistidine concentrations. It was found that Δc_∞ increased hyperbolically with increase in luminal and peritubular histidine concentrations suggesting saturation transport kinetics. Furthermore Δc_∞ declined linearly along the convolution suggesting that nett active transport was not constant throughout the tubule. Using an expression to describe the rate of attainment of steady-state concentration in terms of lummal and peritubular histidine concentrations, histidine permeability coefficient (P), the maximum rate of active histidine transport (J_max) and the half saturation constant of the transport reaction (K_m), we were able to determine the cause of the tubule inhomogeneity. We find that P (14.1×10⁻⁵ cm/s) and J_max (45×10⁻¹⁰ mol/cm²· s) are constant along the convolution but that K_m increases markedly from about 5.4 mmol/kg 26% of the way along the convolution to 40 mmol/kg at 86%. These findings suggest that the histidine reabsorptive mechanism would be relatively inefficient with histidinuria occurring at all plasma concentrations but it would have enormous reserve capacity so that saturation would not readily occur. This prediction accords with available data on histidine clearance in the rat.