Tubular reabsorption of α-aminoisobutyric acid in the pre-steady-state. Evidence for a cell-to-lumen flux

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Abstract
We investigated time-dependent and concentration-dependent renal handling of α-aminoisobutyric acid (AIB) in the rat during seven consecutive 30-min clearance periods after onset of AIB infusion. Following low-level rapid venous infusion of AIB (9.75 μmol/kg in 30 s), plasma [AIB] fell exponentially in the initial three periods and in linear fashion (−0.00158 μM/min) thereafter. Although filtered AIB fell in proportion to plasma [AIB] during the early clearance periods (5–125 min), fractional excretion of AIB (FEAIB) rose (Δ FEAIB = +0.077 ± 0.010, mean ± SD) and stabilized only in later clearance periods (125–215 min). Saturable intrarenal binding does not explain rising FEAIB with falling plasma [AIB] because sequential infusions of AIB, 120 min apart, also elicited the phenomenon after each infusion. During continuous infusions of AIB, time dependence of FEAIB was also observed, in the early interval (5–95 min), after onset of AIB infusion at various concentrations of plasma [AIB] below 3 mM approximately. Measurement of concentration-dependent net tubular reabsorption of AIB in the fourth through seventh clearance periods (near the steady state) revealed progressive saturation over the whole range of plasma [AIB] (0–12 mM), yet with a collapse of net reabsorption in the plasma [AIB] range 2–4 mM. Measurements of renal tissue AIB in these experiments revealed that cellular AIB is of sufficient magnitude and bears such a relationship to plasma AIB and FEAIB that it could contribute to an observable cell-to-lumen movement of amino acid in the "pre-steady-state" situation and could account for the rise in FEAIB following AIB infusion and the collapse in tubular reabsorption of AIB at 2–4 mM plasma [AIB].

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