2863325

Excitatory amino acids: studies on the biochemical and chemical stability of ibotenic acid and related compounds.

Article date: 1985/9/1

PubMed ID: 2863325

Journal name: Journal of neurochemistry (ISSN: 0022-3042)

ABSTRACT

The complex pharmacological profile (excitation/inhibition) of ibotenic acid on single neurons in the mammalian CNS prompted studies on the stability of ibotenic acid and a number of structurally related excitatory amino acids under different in vitro conditions in the presence or absence of enzymes. Ibotenic acid, (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-7-carboxylic acid (7-HPCA), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and (RS)-alpha-amino-3-hydroxy-4-bromo-5-isoxazolepropionic acid (4-Br-homoibotenic acid) were all inhibitors of (S)-glutamic acid decarboxylase (GAD) in mouse brain homogenates, but only ibotenic acid was shown to undergo decarboxylation during incubation with brain homogenates. The formation of the decarboxylated product, muscimol, which primarily occurred in a synaptosomal fraction, was dependent on the presence of pyridoxal-5-phosphate (PALP) and was inhibited by (S)-glutamic acid, 3-mercaptopropionic acid (3MPA), aminooxyacetic acid (AOAA), and allyglycine, suggesting that ibotenic acid is a substrate for GAD. The overall decomposition rate for ibotenic acid (8.7 nmol min-1 mg-1 of protein), which apparently embraces other reactions in addition to decarboxylation to muscimol, was higher than the rate of decarboxylation of (S)-glutamic acid (3.2 nmol min-1 mg-1 of protein). At pH 7.4 and 37 degrees C, but in the absence of enzymes, none of the excitatory amino acids under study underwent any detectable decomposition, whereas ibotenic acid and 7-HPCA, but not AMPA and 4-Br-homoibotenic acid, decomposed, partially by decarboxylation, at 100 degrees C in a pH-dependent manner. In the presence of liver homogenates, ibotenic acid was also shown to decompose.(ABSTRACT TRUNCATED AT 250 WORDS)

This document is available from: http://directlinks.cc/files/muscimol/2863325.pdf

Author List: Nielsen E O, Schousboe A, Hansen S H, Krogsgaard-Larsen P

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Glutamates; Isoxazoles; Oxazoles; Pregnancy Proteins; Ibotenic Acid; Muscimol; Glutamic Acid; 3-hydroxy-4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridine-7-carboxylic acid; gaboxadol;

Mesh terms: Animals; Brain/drug effects; Chemical Phenomena; Chemistry; Chromatography, High Pressure Liquid; Decarboxylation; Glutamates/pharmacology; Glutamic Acid; Hot Temperature; Hydrogen-Ion Concentration; Ibotenic Acid/analogs & derivatives; Isoxazoles/isolation & purification; Liver/drug effects; Mice; Muscimol/isolation & purification; Oxazoles/metabolism; Pregnancy Proteins/pharmacology;

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