title: [3H]norepinephrine release from hippocampal slices is an in vitro biochemical tool for investigating the pharmacological properties of excitatory amino acid receptors.
abstract: [3H]Norepinephrine ([3H]NE) efflux from preloaded rat hippocampal slices was increased in a dose-dependent manner by excitatory amino acids, with the following order of potencies: N-methyl-D-aspartate (NMDA) greater than kainic acid (KA) greater than L-glutamate greater than or equal to D,L-homocysteate greater than L-aspartate greater than quinolinic acid greater than quisqualic acid. The effect of the excitatory amino acids was blocked by physiological concentrations of Mg2+, with the exception of KA. D,L-2-Amino-7-phosphonoheptanoic acid dose-dependently inhibited the NMDA effect (ID50 = 69 microM), whereas at 1 mM it was ineffective versus KA. The release of [3H]-NE induced by quinolinic acid was blocked by 0.1 mM D,L-2-amino-7-phosphonohepatanoic acid. gamma-D-Glutamylglycine dose-dependently inhibited the KA effect with an ID50 of 1.15 mM. Tetrodotoxin (2 microM) reduced by 40 and 20% the NMDA and KA effects, respectively. The data indicate that [3H]NE release from hippocampal slices can be used as a biochemical marker for pharmacological investigations of excitatory amino acid receptors and their putative agonists and antagonists.
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate; D009638:Norepinephrine / Q000378:metabolism*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D004151:Dipeptides; D005971:Glutamates; D011805:Quinolinic Acids; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D006710:Homocysteine; C007956:homocysteic acid; C028929:gamma-glutamylglycine; D001224:Aspartic Acid; D018698:Glutamic Acid; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D017378:Quinolinic Acid; D008274:Magnesium; C031231:2-amino-7-phosphonoheptanoic acid; D007608:Kainic Acid; D009638:Norepinephrine