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Renal balance of pterin cofactors in the rat

A clearance and micropuncture study

  • Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands
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Abstract

In rat kidney, the rate of urinary biopterin [biopterin (B), 7,8-dihydrobiopterin (BH2), and 5,6,7,8-tetrahydrobiopterin (BH4)] excretion as measured by Crithidia assay, was found to be at least 3 times greater than the rate at which it is filtered (GFR·PBiopt.). At a renal blood flow of 6.43±1.34 ml/min per g kidney wt., biopterin concentrations in arterial and renal venous blood and plasma were similar [art. blood: 250±50 ng/ml, ren. venous blood: 247.3±50.9 ng/ml, art. plasma: 23.1±5.8 ng/ml, ren. venous plasma: 23.4±6.9 ng/ml (means±S.D.)].

14C-BH4 and3H-inulin, infused by means of a micropump into late proximal segments of single nephrons at concentrations of 10−4–10−6 mol, were excreted at similar fractional rates (inulin: 0.85–0.97, BH4: 0.87–0.92, total recovery 1.00–1.09 and 0.99–1.11, respectively). Similar results were obtained with 6,7-dimethylpterin, but not with 6,7-dimethyl-5,6,7,8-tetrahydropterin. The latter is reabsorbed at a fractional rate of 0.20 at concentrations of 10−7 and 10−6 mol.

In microperfusion studies in isolated proximal tubular segments in vivo et situ, no reabsorption of 6,7-dimethylpterin could be detected. In case of 6,7-dimethyl-5,6,7,8-tetrahydropterin (DMPH4) at concentrations of 5·10−5 and 10−5 mol/l, however, a permeability constant of 2.39·10−5 cm/s has been measured.

From the fact that more biopterin leaves the kidney with urine plus venous blood than entered it is concluded that reduced biopterin is synthesized de novo in the kidney. With the exception of DMPH4, all types of biopterin are not significantly reabsorbed, but rather, are excreted into the urine due to an anisotropic permeability characteristic of the nephron.

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Häberle, D.A., Schiffl, H., Mayer, G. et al. Renal balance of pterin cofactors in the rat. Pflugers Arch. 375, 9–16 (1978). https://doi.org/10.1007/BF00584142

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