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
Long-term systemic administration of kynurenic acid brain region specifically elevates the abundance of functional CB1 receptors in rats
Ferenc Zádor,Gábor Nagy-Grócz,Szabolcs Dvorácskó,Zsuzsanna Bohár,Edina Katalin Cseh,Dénes Zádori,Árpád Párdutz,Edina Szűcs,Csaba Tömböly,Anna Borsodi,Sándor Benyhe,László Vécsei +11 more
TL;DR: KYNA indirectly and brain region specifically increases the abundance of functional CB1Rs, without modifying the overall binding and activity of the receptor, as a compensatory mechanism on the part of the endocannabinoid system induced by the long-term KYNA exposure.
Journal ArticleDOI
Increased Blood Quinolinic Acid after Exercise in Mice: Implications for Sensation of Fatigue after Exercise
TL;DR: Blood QUIN levels are increased after exercise and that this effect occurs through enhanced tryptophan metabolism in the kynurenine pathway due to TNF-α production, implying that QUIN participates in the sensation of fatigue after exercise.
Journal ArticleDOI
Inflammation associated with chronic heart failure leads to enhanced susceptibility to depression.
Jing Su,Jing Su,Jinghui Wang,Yuanyuan Ma,Qing Li,Yufang Yang,Li Huang,Haoyue Wang,Heng Li,Zishan Wang,Jiabin Tong,Dongping Huang,Xiaochen Bai,Mei Yu,Liping Bu,Jian Fei,Fang Huang +16 more
TL;DR: The results suggest that long‐term CHF increases inflammatory responses in the central nervous system and leads to depression in Sus mice.
Journal ArticleDOI
B7 Costimulation and Intracellular Indoleamine 2,3-Dioxygenase Expression in Umbilical Cord Blood and Adult Peripheral Blood
Enikő Grozdics,László Berta,Béla Gyarmati,Gábor Veres,Dénes Zádori,Levente Szalárdy,László Vécsei,Tivadar Tulassay,Gergely Toldi +8 more
TL;DR: Alterations in the expression of B7 costimulatory molecules and their receptors, as well as differences in the tryptophan (TRP) catabolic pathway, may influence immunological reactivity of umbilical cord blood (UCB) compared with adult peripheral blood (APB) T lymphocytes.
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
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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.