Clearance and stop-flow studies on histidine and methyldopa transport by rat kidney

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Abstract
Endogenous histidine clearances were measured in anesthetized rats undergoing osmotic diuresis following iv infusion of 8% creatinine (as in osmotic diuretic) and 10-100 mmoles/l L-histidine-mono-hydrochloride. A range of plasma histidine concentrations from 1 to 10 mmoles/l was obtained. The renal tubular reabsorption of the amino acid was greater than 97.5% below a plasma histidine concentration of 5 mmoles/l. Stop-flow analysis of renal tubular function localized histidine reabsorption to the proximal tubule and showed active reabsorption against a concentration gradient. The infusion of L-methyldopa (100 mmoles/l) caused an increase in histidine clearance throughout the range of plasma histidine concentrations studied (1-7 mmoles/l). D-Methyldopa was without effect on histidine clearance. Stop-flow studies suggested that L-methyldopa acted by inhibiting histidine reabsorption in the proximal tubule. Stop-flow studies on the transport of methyldopa itself demonstrated net tubular reabsorption by a weak tubular reabsorptive process probably located in the proximal tubule. These findings supported the initial hypothesis that the amina aciduria produced by methyldopa was of a "mixed" type due to saturation of a renal tubular reabsorptive mechanism for methyldopa (and its methoxy metabolite) and to inhibition of the reabsorption of natural amino acids by the synthetic methyldopa.

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