The putative endogenous convulsant 3-hydroxykynurenine decreases benzodiazepine receptor binding affinity: implications to seizures associated with neonatal vitamin B-6 deficiency.
The kynurenines, endogenous tryptophan metabolites with convulsant properties, have been postulated to play a role in the genesis of seizure disorders. We have previously reported that concentrations of 3-hydroxykynurenine (3-HK) higher than 0.2 mM are present in the brains of neonatal rats perinatally deprived of vitamin B-6. At a 1 mM concentration 3-HK significantly decreased the affinity of 3H-flunitrazepam for benzodiazepine receptor sites in rat brain membrane preparations. Furthermore, lower concentrations (Ki = 250 microM) of 3-HK antagonized the enhancing effect of GABA on 3H-flunitrazepam binding. These results suggest that 3-HK may have a modulatory effect on the GABA/benzodiazepine/barbiturate receptor complex.
Guilarte
T R
TR
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205.
Block
L D
LD
Wagner
H N
HN
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003292:Convulsants / Q000494:pharmacology*; D005445:Flunitrazepam / Q000378:metabolism; D007700:Kinetics; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012640:Seizures / Q000503:physiopathology*; D026681:Vitamin B 6 Deficiency / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D003292:Convulsants; D011963:Receptors, GABA-A; C005045:3-hydroxykynurenine; D007737:Kynurenine; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam