Utilization of the synthetic phosphagen cyclocreatine phosphate by a simple brain model during stimulation by neuroexcitatory amino acids.
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 mM cyclocreatine for 90 min, resulting in accumulation of 100 mumol/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 microM), N-methyl-DL-aspartate (20 microM), L-homocysteate (20 microM), L-glutamate (200 microM), D-glutamate (200 microM), L-aspartate (2 mM), DL-2-amino-3-phosphonopropionate (2 mM), and DL-2-amino-4-phosphonobutyrate (2 mM). 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.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology*; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002642:Chick Embryo; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D048289:Imidazolidines; D007608:Kainic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D016202:N-Methylaspartate; D010725:Phosphocreatine / Q000031:analogs & derivatives* / Q000378:metabolism
D000596:Amino Acids; D000613:Aminobutyrates; D005971:Glutamates; D048289:Imidazolidines; D010725:Phosphocreatine; C000211:2-amino-3-phosphonopropionic acid; D006710:Homocysteine; C007956:homocysteic acid; D001224:Aspartic Acid; D018698:Glutamic Acid; C012487:phosphocyclocreatine; D000244:Adenosine Diphosphate; D016202:N-Methylaspartate; D000255:Adenosine Triphosphate; C012729:2-amino-4-phosphonobutyric acid; D008274:Magnesium; D000409:Alanine; D007608:Kainic Acid