Blood-brain barrier transport of kynurenines: implications for brain synthesis and metabolism

J Neurochem. 1991 Jun;56(6):2007-17. doi: 10.1111/j.1471-4159.1991.tb03460.x.


To evaluate the potential contribution of circulating kynurenines to brain kynurenine pools, the rates of cerebral uptake and mechanisms of blood-brain barrier transport were determined for several kynurenine metabolites of tryptophan, including L-kynurenine (L-KYN), 3-hydroxykynurenine (3-HKYN), 3-hydroxyanthranilic acid (3-HANA), anthranilic acid (ANA), kynurenic acid (KYNA), and quinolinic acid (QUIN), in pentobarbital-anesthetized rats using an in situ brain perfusion technique. L-KYN was found to be taken up into brain at a significant rate [permeability-surface area product (PA) = 2-3 x 10(-3) ml/s/g] by the large neutral amino acid carrier (L-system) of the blood-brain barrier. Best-fit estimates of the Vmax and Km of saturable L-KYN transfer equalled 4.5 x 10(-4) mumol/s/g and 0.16 mumol/ml, respectively. The same carrier may also mediate the brain uptake of 3-HKYN as D,L-3-HKYN competitively inhibited the brain transfer of the large neutral amino acid L-leucine. For the other metabolites, uptake appeared mediated by passive diffusion. This occurred at a significant rate for ANA (PA, 0.7-1.6 x 10(-3) ml/s/g), and at far lower rates (PA, 2-7 x 10(-5) ml/s/g) for 3-HANA, KYNA, and QUIN. Transfer for KYNA, 3-HANA, and ANA also appeared to be limited by plasma protein binding. The results demonstrate the saturable transfer of L-KYN across the blood-brain barrier and suggest that circulating L-KYN, 3-HKYN, and ANA may each contribute significantly to respective cerebral pools. In contrast, QUIN, KYNA, and 3-HANA cross the blood-brain barrier poorly, and therefore are not expected to contribute significantly to brain pools under normal conditions.

MeSH terms

  • Animals
  • Biological Transport
  • Blood-Brain Barrier*
  • Brain / metabolism*
  • Kynurenic Acid / pharmacokinetics
  • Kynurenine / analogs & derivatives
  • Kynurenine / chemistry
  • Kynurenine / pharmacokinetics*
  • Male
  • Quinolinic Acid
  • Quinolinic Acids / pharmacokinetics
  • Rats
  • Rats, Inbred Strains
  • ortho-Aminobenzoates / pharmacokinetics


  • Quinolinic Acids
  • ortho-Aminobenzoates
  • anthranilic acid
  • 3-hydroxykynurenine
  • Kynurenine
  • Quinolinic Acid
  • Kynurenic Acid