title: Heterocarrier-mediated reciprocal modulation of glutamate and glycine release in rat cerebral cortex and spinal cord synaptosomes.
abstract: The effects of glutamic acid (Glu) and glycine (Gly) on each others release were studied using rat brain cortex and spinal cord synaptosomes. Previously taken up [3H]Gly and [3H]D-aspartic acid ([3H]D-Asp) was employed as markers for Gly and Glu/Asp release, respectively. Glu enhanced the release of [3H]Gly (EC50 = 8.4 microM) from cortical synaptosomes. The effect of Glu was not mimicked by the glutamate receptor agonists N-methyl-D-aspartic acid (NMDA), kainic or quisqualic acid. The Glu effect was abolished by the Glu/Asp uptake inhibitor D-threo-hydroxy-aspartic acid and it was Na+ sensitive. D-Asp also increased [3H]Gly release (EC50 = 9.9 microM) and the effect was blocked by the Glu/Asp uptake inhibitor. In contrast to its effect in the cortex, Glu failed to increase the release of [3H]Gly from spinal cord synaptosomes. Gly enhanced the outflow of [3H]D-Asp from rat cerebral cortex and spinal cord synaptosomes (EC50 = 75.0 and 99.5 microM, respectively). Gly was much more potent a releaser of [3H]D-Asp in the spinal cord than in the cortex. The Gly effects were insensitive to strychnine or to 7-Cl-kynurenic acid, antagonists at the two known Gly receptors, but they were strongly Na+ dependent. Our results are compatible with the idea that high-affinity uptake systems specific for Glu/Asp or Gly are colocalized on the same nerve terminal in rat spinal cord and cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bonanno
authors.forename: F
authors.initials: F
authors.lastname: Vallebuona
authors.forename: F
authors.initials: F
authors.lastname: Donadini
authors.forename: G
authors.initials: G
authors.lastname: Fontana
authors.forename: E
authors.initials: E
authors.lastname: Fedele
authors.forename: M
authors.initials: M
authors.lastname: Raiteri
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000378:metabolism* / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D012964:Sodium; D007608:Kainic Acid; D005998:Glycine