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Related Experiment Videos

Renal metabolic/excretory coupling.

L A Spry1, J Rubinstein, C Rettke

  • 1Veterans Administration Medical Center, GRECC, St. Louis, MO 63125.

The American Journal of Physiology
|January 1, 1988
PubMed
Summary
This summary is machine-generated.

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Renal metabolism enhances the excretion of nitrofurothiazoles like FANFT. This process, involving deformylation to ANFT, significantly increases ANFT

Area of Science:

  • Pharmacology and Toxicology
  • Renal Physiology
  • Drug Metabolism

Background:

  • Renal metabolic/excretory coupling describes how kidney metabolism boosts urinary excretion.
  • Nitrofurothiazoles, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) and 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT), serve as model compounds for studying this phenomenon.
  • FANFT undergoes deformylation to ANFT by renal deformylase, which enhances ANFT's excretion.

Purpose of the Study:

  • To investigate the mechanism of renal metabolic/excretory coupling using FANFT and ANFT.
  • To characterize the uptake kinetics of FANFT and ANFT in renal tubules.
  • To determine the properties and kinetics of renal deformylase involved in FANFT metabolism.

Main Methods:

  • Oral administration of FANFT and ANFT in rats to compare excretion rates.

Related Experiment Videos

  • In vitro uptake studies of FANFT and ANFT into purified proximal tubules and oil.
  • Assay of renal deformylase activity, including kinetic parameter determination (Km, Vmax) and characterization of its properties.

    • Main Results:

    • Oral FANFT administration resulted in a 100-fold greater ANFT excretion compared to direct ANFT administration in rats.
    • FANFT and ANFT exhibited rapid uptake into proximal tubules (equilibrium within 60s), which occurred even in nonviable tubules.
    • Albumin significantly inhibited uptake, and tubular FANFT uptake was substantially higher than ANFT uptake.
    • Renal deformylase was primarily cytosolic, with specific kinetic properties (Km 6.7 µM, Vmax 6.1 nmol/min/mg protein), and demonstrated specificity for N-formylated compounds.

    Conclusions:

    • Renal metabolic/excretory coupling for FANFT/ANFT involves energy-independent uptake coupled with metabolic deformylation.
    • This process significantly enhances urinary excretion of ANFT.
    • The findings elucidate a key mechanism in renal drug handling and excretion.