Hindlimb paralytic effects of prodynorphin-derived peptides following spinal subarachnoid injection in rats

Joseph B. Long, Alberto Martinez-Arizala, Eddie E. Echevarria, Raymond E. Tidwell, John W. Holaday

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Dynorphin A-(1-17) acts through non-opioid mechanisms to produce dose-related neurological deficits following injection into the lumbar spinal subarachnoid space in rats. Hindlimb motor function was examined following subarachnoid injection of dynorphin A fragments and other opioid peptides derived from prodynorphin to establish: (1) which portion(s) of the dynorphin A molecule cause hindlimb motor dysfunction, and (2) whether these paralytic actions are shared by other opioids (dynorphin B, α-neo-endorphin, and β-neo-endorphin) derived from the same promolecule. To minimize the influence of enzymatic inactivation on relative bioactivities, peptides were coinjected with a combination of peptidase inhibitors previously shown to enhance the actions of dynorphin A fragments in vitro. Dynorphin A-(1-17) and -(2-17) produced dose-related neurological deficits with equal potencies and durations. Although without effect when injected alone, dynorphin A-(1-8), -(1-7) and -(3-8) caused transient motor dysfunction when co-injected with peptidase inhibitors. In contrast, dynorphin A-(1-6), -(1-5) and -(6-17) did not disrupt hindlimb motor function with or without peptidase inhibition. Dynorphin B, α-neo-endorphin also caused hindlimb dysfunction which was potentiated by peptidase inhibition. These deficits appeared to result from non-opioid actions of these three peptides, since they were not blocked by the opioid antagonist naloxone. Thus, the paralytic effects of dynorphin A: (1) result from non-opioid actions involving the 3-7 or 3-8 positions of the molecule, and (2) are shared by other prodynorphin-derived opioid peptides.

Original languageEnglish (US)
Pages (from-to)45-54
Number of pages10
JournalEuropean Journal of Pharmacology
Volume153
Issue number1
DOIs
StatePublished - Aug 9 1988
Externally publishedYes

Keywords

  • (Paralysis, Injury, Intrathecal)
  • Dynorphin A
  • Dynorphin B
  • Opiate receptors
  • Peptidase
  • Spinal cord
  • α-neo-Endorphin
  • β-neo-Endorphin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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