Amino acids as central nervous transmitters: the influence of ions, amino acid analogues, and ontogeny on transport systems for L glutamic and L aspartic acids and glycine into central nervous synaptosomes of the rat

J. P. Bennett, W. J. Logan, Solomon H Snyder

Research output: Contribution to journalArticle

Abstract

The accumulation by synaptosomal fractions from rat central nervous system tissue of transmitter candidate amino acids and non candidate amino acids was studied with respect to ionic requirements, metabolic inhibitors, structural analogues, and ontogeny. For L glutamic and L aspartic acids in cortex and spinal cord and glycine in spinal cord a stringent sodium requirement for high affinity uptake was demonstrated. Detailed kinetic analysis of the sodium requirement for glutamic acid uptake into cortical synaptosomal fractions suggests that: sodium ion acts both competitively and noncompetitively in determining the velocity of high affinity uptake; in the absence of sodium ion only the low affinity uptake can be demonstrated; and inhibition of the Na K ATPase enzyme system with ouabain reduces the velocity of uptake to 60% of control values in contrast to alanine whose synaptosomal uptake is less dependent on this enzyme system. No potent inhibitors of L glutamic acid accumulation were found among several structural analogues or derivatives. The kinetic analysis for glycine accumulation was more complex and suggested allosteric interactions between glycine and sodium ion. Developmental studies revealed GABA and L glutamic acid to have absolute sodium requirements for cortical synaptosomal accumulation from the 16th gestational day through adulthood, with glycine accumulation showing a decreasing sodium requirement as maturation proceeded over this period. The combined evidence suggests that sodium requirement for high affinity uptake is a characteristic of neuroactive substances and may be used as a screening tool to search for other neurotransmitter candidates.

Original languageEnglish (US)
Pages (from-to)1533-1550
Number of pages18
JournalJournal of Neurochemistry
Volume21
Issue number6
StatePublished - 1973

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Synaptosomes
Aspartic Acid
Glycine
Rats
Transmitters
Sodium
Ions
Amino Acids
Glutamic Acid
Spinal Cord
Nerve Tissue
Kinetics
Neurology
Ouabain
Enzymes
Alanine
gamma-Aminobutyric Acid
Neurotransmitter Agents
Adenosine Triphosphatases
Screening

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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title = "Amino acids as central nervous transmitters: the influence of ions, amino acid analogues, and ontogeny on transport systems for L glutamic and L aspartic acids and glycine into central nervous synaptosomes of the rat",
abstract = "The accumulation by synaptosomal fractions from rat central nervous system tissue of transmitter candidate amino acids and non candidate amino acids was studied with respect to ionic requirements, metabolic inhibitors, structural analogues, and ontogeny. For L glutamic and L aspartic acids in cortex and spinal cord and glycine in spinal cord a stringent sodium requirement for high affinity uptake was demonstrated. Detailed kinetic analysis of the sodium requirement for glutamic acid uptake into cortical synaptosomal fractions suggests that: sodium ion acts both competitively and noncompetitively in determining the velocity of high affinity uptake; in the absence of sodium ion only the low affinity uptake can be demonstrated; and inhibition of the Na K ATPase enzyme system with ouabain reduces the velocity of uptake to 60{\%} of control values in contrast to alanine whose synaptosomal uptake is less dependent on this enzyme system. No potent inhibitors of L glutamic acid accumulation were found among several structural analogues or derivatives. The kinetic analysis for glycine accumulation was more complex and suggested allosteric interactions between glycine and sodium ion. Developmental studies revealed GABA and L glutamic acid to have absolute sodium requirements for cortical synaptosomal accumulation from the 16th gestational day through adulthood, with glycine accumulation showing a decreasing sodium requirement as maturation proceeded over this period. The combined evidence suggests that sodium requirement for high affinity uptake is a characteristic of neuroactive substances and may be used as a screening tool to search for other neurotransmitter candidates.",
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T2 - the influence of ions, amino acid analogues, and ontogeny on transport systems for L glutamic and L aspartic acids and glycine into central nervous synaptosomes of the rat

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AU - Logan, W. J.

AU - Snyder, Solomon H

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