Tryptofaanin katabolia soluissa

http://www.biochemj.org/bj/326/0351/bj3260351.htm
Immuuniaktivaation aikana:
 Tryptofaani-kynureeni tien aineenvaihdunnallisissa tuotteissa  on huomattavaa  määrällistä nousua, L-kynureenihappoa ja neurotoksista kinoliinihappoa ilmenee aivojen alueella, veressä  ja systeemisissä kudoksissa.
 Substantial increases in the tryptophan–kynurenine pathway metabolites, L-kynurenine and the neurotoxin quinolinic acid, occur in human brain, blood and systemic tissues during immune activation.
WIKIPEDIA antaa myös laajan näkymän tähän kataboliseen ongelmaan.
 http://en.wikipedia.org/wiki/Quinolinic_acid

Miten tämä suhtautuu esim aivoiskemia tilanteeseen?  Ja miten siihen vastavaikuttaa? Sehän tekee  excitotoksisuutta lisää. Pohdittavaksi tarkemmin jossain välissä.
Tryptofaani on ravintoperäinen molekyyli.

KYNUREENIHAPON vaikutus aivossa:

Biochem Pharmacol. 2012 Oct 15;84(8):1078-87. doi: 10.1016/j.bcp.2012.07.030. Epub 2012 Aug 2.Kynurenic acid inhibits glutamatergic transmission to CA1 pyramidal neurons via α7 nAChR-dependent and -independent mechanisms.

Banerjee J, Alkondon M, Albuquerque EX.

Division of Translational Toxicology, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Abstract

Glutamatergic hypofunction and elevated levels of kynurenic acid (KYNA) in the brain are common features of patients with schizophrenia. In vivo studies indicate that in the hippocampus KYNA decreases glutamate levels, presumably via inhibition of α7 nicotinic receptors (nAChRs). Here we tested the hypothesis that basal synaptic glutamate activity in the hippocampus is regulated by tonically active α7 nAChRs and is sensitive to inhibition by KYNA. To this end, spontaneous excitatory postsynaptic currents (EPSCs), sensitive to AMPA receptor antagonist CNQX (10 μM), were recorded from CA1 pyramidal neurons at -70 mV in rat hippocampal slices. The α7 nAChR antagonists α-bungarotoxin (α-BGT, 100 nM) and methyllycaconitine (MLA, 1-50 nM), and the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV, 50 μM) reduced the frequency of EPSCs. MLA and α-BGT had no effect on miniature EPSCs (mEPSCs). The effect of MLA decreased in the presence of APV (50 μM), with 1 nM MLA becoming completely ineffective. KYNA (1-20 μM) suppressed the frequency of EPSCs, without affecting mEPSCs. The effect of KYNA decreased in the presence of MLA (1 nM) or α-BGT (100 nM), with 1 μM KYNA being devoid of any effect. In the presence of both MLA (10 nM) and APV (50 μM) higher KYNA concentrations (5-20 μM) still reduced the frequency of EPSCs. These results suggest that basal synaptic glutamate activity in CA1 pyramidal neurons is maintained in part by tonically active α7 nAChRs and NMDA receptors and is inhibited by micromolar concentrations of KYNA, acting via α7 nAChR-dependent and -independent mechanisms.
Copyright © 2012 Elsevier Inc. All rights reserved.