Journal ArticleDOI
Blood–Brain Barrier Transport of Kynurenines: Implications for Brain Synthesis and Metabolism
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TLDR
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 under normal conditions.Abstract:
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.read more
Citations
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Journal ArticleDOI
Quantitative profiling of neurotransmitter abnormalities in brain, cerebrospinal fluid, and serum of experimental diabetic encephalopathy male rat.
Xiaowen Han,Mengjun Min,Juan Wang,Zejun Bao,Hongbin Fan,Xinyu Li,Temitope Isaac Adelusi,Xueyan Zhou,Xiaoxing Yin +8 more
TL;DR: A quantitative method is established for the simultaneous detection of tryptophan and its metabolites in streptozotocin‐induced experimental DE rats and a critical elucidation of the nervous system dysfunction in DE is presented.
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Kynurenic Acid Metabolism in Various Types of Brain Pathology in HIV-1 Infected Patients.
TL;DR: Interestingly, a marked enhancement of kynurenic acid metabolism in the brain has been found with occurrence of bronchopneumonia, and this finding indicates a notable association between impaired conditions of oxygen availability and enhancement of l-kynurenine formation in the human brain.
Journal ArticleDOI
Activation of the kynurenine pathway and mitochondrial respiration to face allostatic load in a double-hit model of stress.
Verena Nold,C. Sweatman,Alexander Karabatsiakis,Christina Böck,Tom Bretschneider,Nathan Lawless,K. Fundel-Clemens,Iris-Tatjana Kolassa,Kelly A. Allers +8 more
TL;DR: It is suggested that early life adversity may impact on allostatic load by increasing energetic requirements in the brain by triggering a protective, anti-oxidant response from the kynurenine pathway.
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Cerebrospinal fluid kynurenic acid in male patients with schizophrenia - correlation with monoamine metabolites
TL;DR: The results of this study suggest that increased KYNA formation is associated with an increased dopamine and serotonin turnover in male patients with schizophrenia.
Journal ArticleDOI
Determination of kynurenic acid by capillary electrophoresis with laser-induced fluorescence detection.
TL;DR: A method for the determination of KA in microdialysate samples using capillary electrophoresis (CE) separation with laser-induced fluorescence (LIF) detection is described, which could be used to monitor the increase in KA levels in rat brain following dosing with its precursors, tryptophan and kynurenine.
References
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Journal ArticleDOI
Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain
TL;DR: Intracerebral injection of the neuroexcitatory tryptophan metabolite, quinolinic acid, has behavioral, neurochemical and neuropathological consequences reminiscent of those of exogenous excitotoxins, such as kainic and ibotenic acids.
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Distinct mediating systems for the transport of neutral amino acids by the ehrlich cell
Journal ArticleDOI
Amino acid assignment to one of three blood-brain barrier amino acid carriers
William H. Oldendorf,John Szabo +1 more
TL;DR: Affinity for a basic amino acid carrier system was demonstrated for arginine, ornithine, and lysine and a third, low-capacity independent carrier system transporting aspartic and glutamic acids was demonstrated.
Journal ArticleDOI
An in situ brain perfusion technique to study cerebrovascular transport in the rat
TL;DR: The in situ brain perfusion technique is a sensitive new method to study cerebrovascular transfer in the rat and permits absolute control of perfusate composition.