PMID: 11343833May 10, 2001Paper

Excitotoxic injury stimulates pro-drug-induced 7-chlorokynurenate formation in the rat striatum in vivo

Neuroscience Letters
S C Lee, R Schwarcz

Abstract

Peripheral administration of L-4-chlorokynurenine (4-Cl-KYN), which is enzymatically converted in astrocytes to form the glycine(B) receptor antagonist 7-chlorokynurenic acid (7-Cl-KYNA), has been shown to provide neuroprotection against excitotoxic damage. The present study was designed to examine the metabolic fate of 4-Cl-KYN after systemic injection, and to study its brain uptake and subsequent transamination during the acute phase following an excitotoxic insult. To this end, adult rats received intrastriatal injections of vehicle (1 microl) or quinolinic acid (QUIN) (240 nmol/1 microl), and were administered 50 mg/kg 4-Cl-KYN (intraperitoneally) immediately after surgery. After 90 and 180 min, 7-Cl-KYNA concentrations in the vehicle-injected striatum were 54+/-13 and 16+/-2 nM, respectively. The contralateral, QUIN-injected striatum contained 212+/-39 and 97+/-27 nM 7-Cl-KYNA, respectively. This injury-induced increase was accompanied by slightly higher 4-Cl-KYN levels in the QUIN-treated striatum, indicating that better pro-drug availability in part accounts for the enhanced 7-Cl-KYNA formation. These data demonstrate that systemic 4-Cl-KYN application, by targeting reactive glial cells during the early, reversible stage...Continue Reading

References

May 11, 1992·Annals of the New York Academy of Sciences·R SchwarczR C Roberts
Jul 1, 1988·Journal of Neurochemistry·F MoroniV Carlà
Jan 1, 1988·Experimental Brain Research·W A Turski, R Schwarcz
Nov 25, 1994·Journal of Medicinal Chemistry·P D Leeson, L L Iversen
Jan 1, 1994·Annual Review of Neuroscience·D M Landis
Feb 4, 1994·Journal of Medicinal Chemistry·F G SalituroR Schwarcz
Apr 1, 1996·Progress in Neurobiology·J G Greene, J T Greenamyre
Feb 4, 1999·Journal of Neurochemistry·P S HodgkinsR Schwarcz
Jul 7, 1999·Journal of Neural Transmission·G Ceresoli-BorroniR Schwarcz

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Citations

Apr 22, 2017·The Journal of Pain : Official Journal of the American Pain Society·Tony L YakshH Ralph Snodgrass
Sep 19, 2018·Expert Opinion on Therapeutic Targets·Radhika SharmaAnurag Kuhad
Aug 13, 2015·The Journal of Pharmacology and Experimental Therapeutics·Panos ZanosTodd D Gould
Sep 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Robert Schwarcz, Roberto Pellicciari
Nov 3, 2020·ENeurologicalSci·Dhivya VenkatesanBalachandar Vellingiri

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