Alterations of Amino Acid Transmitter Systems in Spinal Cords of Chronic Paraplegic Dogs

W. J. McBride, P. V. Hall, E. Chernet, J. T. Patrick, S. Shapiro

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The high-affinity uptake of [3H]serotonin, [3H]glutamate, and [3H]γ-aminobutyric acid ([3H]GABA) and the Na+-independent binding of [3H]glutamate and [3H]GABA were studied using spinal cord preparations obtained from normal mongrel dogs and from dogs made paraplegia by midthoracic spinal cord crush. Lumbosacral regions of the spinal cord were removed either before (1 week) or after (3 to 8 weeks) onset of spasticity. A myelin-free synaptosomal fraction was obtained by centrifugation and used for studying high-affinity uptake and for preparing synaptic plasma membranes for Na+-independent binding experiments. For the paraplegic groups, the uptake of 30 nM [3H]serotonin was 66 and 18% of control values after 1 and 3 weeks, respectively. Eadie-Hofstee analysis of [3H]serotonin uptake showed a 90% reduction in V(max) for the paraplegic group relative to control values, thereby indicating the expected loss of descending serotonergic pathways. The high-affinity uptakes of 1 μM [3H]glutamate and [3H]GABA were the same in both the control and nonspastic paraplegic groups after 1 week. However, after 3 weeks, the uptakes of [3H]glutamate and [3H]GABA were 60-70% higher for the spastic group than for the control animals. For both amino acids, Eadie-Hofstee plots revealed no difference in K(m) and higher V(max) for the spastic group relative to control values. After 1 and 3 weeks, the Na+-independent binding of 5 nM [3H]glutamate was 40-85% higher and the binding of 10 nM [3H]GABA was 40-60% lower for the paraplegic groups relative to the values for the control animals. Scatchard analysis revealed significant changes in B(max) values for both amino acids. Overall, the data indicate an increase in segmental amino acid excitatory influence which occurred when signs of spasticity were evident.

Original languageEnglish (US)
Pages (from-to)1625-1631
Number of pages7
JournalJournal of Neurochemistry
Volume42
Issue number6
DOIs
StatePublished - Jun 1984

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Keywords

  • GABA
  • Glutamate
  • Paraplegic
  • Serotonin
  • Spasticity
  • Spinal cord

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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