Premium
Presence of 3‐Hydroxyanthranilic Acid in Rat Tissues and Evidence for Its Production from Anthranilic Acid in the Brain
Author(s) -
Baran Halina,
Schwarcz Robert
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb04553.x
Subject(s) - endocrinology , medicine , cerebral cortex , chemistry , cortex (anatomy) , thalamus , anthranilic acid , biology , biochemistry , neuroscience
As assessed by HPLC with electrochemical detection, 3‐hydroxyanthranilic acid (3‐HANA) was found to be present in the rat brain and peripheral organs. The highest concentrations were measured in the kidney (86 fmol/mg of tissue) and spleen (56 fmol/mg of tissue), whereas the adrenal gland, liver, heart, and several forebrain areas (hippocampus, striatum, parietal cortex, thalamus, amygdala/pyriform cortex, and frontal cortex) contained less 3‐HANA (between 15 and 22 fmol/mg of tissue). Slightly lower concentrations of 3‐HANA were found in the brainstem and the cerebellum. The metabolic disposition of 3‐HANA was examined in tissue slices which were incubated in Krebs‐Ringer buffer at 37°C in vitro. Incubation for up to 2 h did not affect 3‐HANA concentration in brain tissue. However, inhibition of 3‐HANA degradation by the specific 3‐hydroxyanthranilic acid oxygenase blocker 4‐chloro‐3‐hydroxyanthranilic acid (4‐C1‐3‐HANA; 10 μ M ) resulted in a rapid (within 2.5 min) doubling of 3‐HANA levels in slices from cerebral cortex. No further increases were observed after incubations of up to 120 min. Exposure of cortical slices to 3‐HANA's putative bioprecursors, 3‐hydroxykynurenine (3‐HK) and anthranilic acid (ANA), in the absence of 4‐C1‐3‐HANA resulted in rapid, transient increases in 3‐HANA production. Maximal 3‐HANA synthesis from ANA exceeded the maximal effect of 3‐HK by approximately 11‐fold. In the presence of 4‐C1‐3‐HANA, 1 m M 3‐HK and 1 m M ANA produced 9.0 ± 0.3 and 89.0 ± 9.3 (5 min) or 51.6 ± 7.9 and 187.5 ±11.2 (120 min) fmol of newly synthesized 3‐HANA/mg of brain tissue, respectively. In the brain, but not in the spleen, ANA proved to be a superior 3‐HANA precursor at lower concentrations as well. Time and dose relationships for the de novo production of 3‐HANA from ANA in brain slices were established in the presence of 10 μ M 4‐C1‐3‐HANA. Biosynthesis of 3‐HANA from ANA in the brain may be critically involved in the function or dysfunction of 3‐HANA's principal cata‐bolic product, the endogenous excitotoxin quinolinic acid.