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Presence and Measurement of Imidazoleacetic Acid, a γ‐Aminobutyric Acid Agonist, in Rat Brain and Human Cerebrospinal Fluid
Author(s) -
Khandelwal Jai K.,
Prell George D.,
Morrishow Albert Marcus,
Green Jack Peter
Publication year - 1989
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.1471-4159.1989.tb01854.x
Subject(s) - chemistry , imidazole , derivatization , agonist , ethyl chloroformate , cerebrospinal fluid , receptor , chromatography , biochemistry , stereochemistry , high performance liquid chromatography , medicine
Imidazoleacetic acid (IAA) was unequivocally demonstrated in rat brain, human CSF, and human plasma by a gas chromatographic‐mass spectrometric method that can reliably quantify as little as 8 pmol, i.e., 1 ng. Owing to tautomerism of the imidazole ring, IAA and [ 15 N, 15 N]IAA, the internal standard, each formed two chromatographically distinct isomers after derivatization of the ring nitrogens with either ethyl chloroformate or methyl chloroformate. The isomers of n ‐butyl( N ‐ethoxycarbonyl)imidazole acetate and n ‐butyl( N ‐methoxycarbonyl)imidazole acetate were identified by analysis with methane chemical ionization and electron impact ionization of molecular and fragment ions. The levels (mean ± SEM) of free IAA were 140 ± 14 pmol/g and 2.7 ± 0.2 pmol/ml in brains of untreated rats and human lumbar CSF, respectively. Mean levels of IAA in brains of anesthetized rats, perfused free of blood, did not differ significantly from mean levels of anesthetized, nonperfused controls or from untreated rats. The source or sources of IAA in brain and CSF are unknown. Because IAA is a potent agonist at γ ‐aminobutyrate receptors, it merits examination as a regulator in brain.