Hindlimb paralytic effects of arginine vasopressin and related peptides following spinal subarachnoid injection in the rat

Joseph B. Long, Alberto Martinez-Arizala, Donald D. Rigamonti, John W. Holaday

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Intrathecal (IT) injection of arginine vasopressin (AVP) in rats caused a transient (<30 min), dose-related paralysis of the hindlimbs, loss of hindlimb and tail nociceptive responsiveness, and increased mean arterial pressure. Motor dysfunction was produced with comparable potency by lysine vasopressin (LVP) and arginine vasotocin (AVT); oxytocin (OXY) was approximately 1000 times less potent. Paralysis induced by these peptides was selectively blocked following IT pretreatment with 0.5 nmoles of the vasopressin V1 receptor antagonist [1-(β-mercapto-β,β-cyclopentamethylene propioinic acid), 2-(O-methyl)tyrosine] Arg8-vasopressin (d(CH2)5[Tyr(Me2)]AVP). Pressor and antinociceptive responses to AVP were also blocked by this compound. However, at higher doses (2-5 nmoles, IT), d(CH2)5[Tyr(Me2)]AVP produced hindlimb paralysis, antinociception, and pressor responses by itself. In contrast to the fiber degeneration, cell loss, and necrosis found in lumbosacral cords of rats persistently paralyzed by other peptides (dynorphin A, somatostatin, and ICI 174864), neuropathological changes were not evident in spinal cords of rats transiently paralyzed by IT AVP. These results indicate that AVP-related peptides affected diverse spinal cord functions through interactions with a V1-like receptor. The similar pattern of cardiovascular and antinociceptive responses to other peptides (dynorphin A, somatostatin, and ICI 174864), which also caused hindlimb paralysis, suggests that the former responses may actually reflect the nonselective consequences of a peptide-induced disruption of spinal cord function, rather than specific shared pharmacological effects.

Original languageEnglish (US)
Pages (from-to)1335-1344
Number of pages10
JournalPeptides
Volume9
Issue number6
DOIs
StatePublished - Jan 1 1988
Externally publishedYes

Keywords

  • Antinociception
  • Arterial pressure
  • Injury
  • Oxytocin
  • Paralysis
  • Spinal cord
  • Vasopressin

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

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