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Utilization of the Synthetic Phosphagen Cyclocreatine Phosphate by a Simple Brain Model During Stimulation by Neuroexcitatory Amino Acids
Author(s) -
Woznicki Dennis T.,
Walker James B.
Publication year - 1988
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.1471-4159.1988.tb03054.x
Subject(s) - amino acid , stimulation , kainate receptor , glutamate receptor , biology , excitatory postsynaptic potential , biochemistry , medicine , endocrinology , receptor , ampa receptor
The ability of 1‐carboxymethyl‐2‐imino‐3‐phosphonoimidazolidine (cyclocreatine‐P), accumulated by a simple brain model, to function as a supplemental synthetic phosphagen and respond to the decreases in cytosolic ATP/free ADP ratios that occur during prolonged stimulation by various excitatory amino acids was investigated. Suspensions of chopped whole brain from 11‐ to 14‐day‐old chick embryos were incubated with 30 m M cyclocreatine for 90 min, resulting in accumulation of 100 μmol/g dry weight of cyclocreatine‐P, and then incubated for up to 1 h with a series of excitatory amino acids of widely differing potencies. Under these conditions net utilization of cyclocreatine‐P was detected in response to stimulation by the following neuroexcitatory compounds at the indicated threshold concentrations: kainate (20 μ M ), N ‐methyl‐dl‐aspartate (20 μ M ), l‐homocysteate (20 μ M ), l‐glutamate (200 μ M ), d‐glutamate (200 μ M ), l‐aspartate (2 m M ), dl‐2‐amino‐3‐phosphonopropionate (2 m M ), and dl‐2‐amino‐4‐phosphonobutyrate (2 m M ). Significant increases in water content of chick embryo brain minces accompanied stimulation by excitatory amino acids. It is suggested that changes in water content or cyclocreatine‐P levels in this sensitive brain model might be utilized in automatable screening procedures for detecting novel antagonists and/or new agonists of excitatory amino acids.