Species differences in L-tryptophan-kynurenine pathway metabolism: quantification of anthranilic acid and its related enzymes.
Anthranilic acid (AA) has attracted considerable attention as one of the L-tryptophan-kynurenine pathway metabolites in the central nervous system. In this study, a highly sensitive and accurate method for the quantification of AA has been developed using reversed-phase high-performance liquid chromatography with electrochemical detection. Serum and cerebrospinal fluid (CSF) AA concentrations in different animal species were measured. CSF AA concentrations in rabbits were 1.1 +/- 0.1 nmol/liter, which were 5. 7-33.0 times lower than those in other species studied. Serum AA concentrations, however, were slightly higher in rabbits than in other species. In contrast, the concentrations of L-kynurenine (L-KYN) in both serum and CSF were substantially higher in rabbits than in other species. Tissue kynurenine pathway enzymes, indoleamine 2,3-dioxygenase (IDO), tryptophan 2,3-dioxygenase, kynurenine 3-hydroxylase, and kynureninase were determined in rabbits, rats, gerbils, and mice. These enzymes varied among species, especially lung IDO activities in rabbits were 146-516 times higher than those found in other species, but rabbit liver kynurenine 3-hydroxylase activities were lower by one order of magnitude than those of the other species tested. Furthermore, brain kynurenine 3-hydroxylasae activities were 12.3-23.2 times higher in gerbils than those in the other species tested. In addition, AA concentrations in serum following intravenous administration of L-KYN (5 mg/kg) were also measured in rabbits. AA levels peaked sharply within 5 min after administration and decreased in a time-dependent manner. At 5 min after administration, CSF L-KYN and AA concentrations were also increased by 1.76- and 2.56-fold, respectively, compared with basal levels. Increased AA concentrations in CSF following L-KYN administration may reflect the entry of AA into the CSF after conversion to AA in systemic tissue and/or the local synthesis of AA from L-KYN in the CNS.
Fujigaki
S
S
Department of Laboratory Medicine, Gifu University School of Medicine, Gifu, 40 Tsukasa-machi, 500-8705, Japan.
Saito
K
K
Takemura
M
M
Fujii
H
H
Wada
H
H
Noma
A
A
Seishima
M
M
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D005849:Gerbillinae; D006168:Guinea Pigs; D006801:Humans; D006867:Hydrolases / Q000737:chemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007275:Injections, Intravenous; D007737:Kynurenine / Q000008:administration & dosage / Q000378:metabolism*; D050601:Kynurenine 3-Monooxygenase; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D014364:Tryptophan / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000737:chemistry; D062367:ortho-Aminobenzoates / Q000097:blood / Q000378:metabolism*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D007737:Kynurenine; D014364:Tryptophan; D006899:Mixed Function Oxygenases; D014366:Tryptophan Oxygenase; D050601:Kynurenine 3-Monooxygenase; D006867:Hydrolases; C021480:kynureninase