Cationic amino acid fluxes beyond the proximal convoluted tubule of rat kidney

Stefan Silbernagl, Katharina Völker, William H. Dantzler

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

To investigate the fluxes of cationic amino acids beyond the proximal convolution, we micropunctured and microperfused superficial tubules of male Wistar rats in vivo et situ. In free-flow micropuncture experiments, the concentrations of endogenous L-arginine+, [Arg], and of intravenously infused L-homoarginine+, [HoArg], were determined by HPLC. Fluorescein isothiocyanatelabeled inulin was detected on-line in the same tubular fluid samples. To determine undirectional fluxes, radiolabeled Arg and inulin were (1) microperfused through short loops of Henle and (2) microinfused into different tubule segments to measure urinary recovery of the radiolabel. At a mean [Arg]plasma of 116 μmol/l, [Arg] was 9.3 μmol/l in the late proximal tubule (LPT), and 35.6 μmol/l in the early distal tubule (EDT) corresponding to fractional deliveries (FD) of 0.055 in LPT and 0.078 in EDT. Fractional urinary excretion (FE) of Arg was 0.00033 (P<0.05 vs FDEDT). Infusion of HoArg (2.5 or 7.5 μmol/min) led to respective mean [HoArg]plasma values of 1.44 and 3.73 mmol/l, and resulted in respective FDLPT values for HoArg of 0.23 and 0.53, respective FDEDT values of 0.29 and 0.41, and finally, respective FE values for HoArg of 0.25 and 0.58. When short loops of Henle were microperfused with 1 or 50 mmol/l [14C]Arg (+[3H]inulin), fractional recovery (FR) of 14C (relative to inulin) in the EDT was 0.13 and 0.36, respectively. During microinfusion of radiolabeled Arg (1 or 50 mmol/l) and inulin into LPT, the urinary FR of the radiolabel was 0.14, or 0.59, respectively. If 0.007, 1 or 50 mmol/l radiolabeled Arg were microinfused into EDT, the respective urinary FR of the radioactivity was 1.02, 1.10, or 1.01. Microperfusion of microinfusion of 1 mmol/l [14C]Arg plus 50 mmol/l HoArg resulted in a FREDT of 14C of 0.43 (loop, perfusion) and an FE for 14C of 0.69. Five conclusions can be drawn. First, cationic amino acids can enter and leave the lumen of short loops of Henle through specific carrier(s) at high rates, although, secondly, net transport is small or absent. Thus, medullary tubule cells can be supplied with Arg from the lumen of short loops of Henle for urea and nitric oxide production. Thirdly, the distal convolution of superficial nephrons and the collecting duct are not permeable to Arg. Thus, fourthly, the difference between FDEDT and urinary FE of Arg must be explained by an inter-nephron heterogeneity between deep and superficial nephrons. Finally, the process responsible for the different Arg handling in deep nephrons is not accessible to HoArg or, if so, it is saturated at millimolar concentrations.

Original languageEnglish (US)
Pages (from-to)210-215
Number of pages6
JournalPflügers Archiv European Journal of Physiology
Volume429
Issue number2
DOIs
StatePublished - Dec 1 1994

Keywords

  • Arginine
  • Homoarginine
  • Rat kidney
  • Renal medulla

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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