EFFECTS OF 540C91 [(E)-3-[2-(4'-PYRIDYL)-VINYL]-1H-INDOLE], AN INHIBITOR OF HEPATIC TRYPTOPHAN DIOXYGENASE, ON BRAIN QUINOLINIC ACID IN MICE

Studies were undertaken to assess the role-of the liver in the formati on of the neurotoxin quinolinic acid in the brain. A selective and pot ent inhibitor of hepatic tryptophan 2,3-dioxygenase, 540C91 [(E)-3-[2- (4'-pyridyl)-vinyl]-1H-indole], largely prevented the elevation in mou se brain quinolinic acid resulting from parenteral injection of trypto phan (TRP). In contrast, 540C91 did not affect basal levels of the neu rotoxin. Following induction of indoleamine dioxygenase with bacterial lipopolysaccharide, 540C91 was less effective in preventing the TRP-i nduced elevations in quinolinic acid. The data suggest that kynurenine s, formed from tryptophan, by the liver and other extrahepatic organs can give rise to brain quinolinic acid.