Axotomy-induced ornithine decarboxylase activity in the mouse dorsal root ganglion is inhibited by the vinca alkaloids.
Vinca alkaloids were used to study the role of retrograde axon transport (RT) in activating neuron perikaryal repair response to nerve transection. Mouse lumbar dorsal root ganglia (DRG) (L4-L6) were excised 48 hours after unilateral transection of the sciatic nerve and ornithine decarboxylase (ODC) activity determined. ODC activity in DRG ipsilateral to nerve transection was increased 10-20 fold over contralateral values. Typical ODC activities in ipsilateral and contralateral DRG samples were 6.18 +/- 1.4 and 0.31 +/- 0.09 pmol 14CO2 released/h/3DRG, respectively. Systemic administration of single doses of either vincristine (1 mg/kg) or vinblastine (5 mg/kg) immediately prior to axotomy attenuated ODC induction in ipsilateral DRG by 39% and 47%, respectively. A direct inhibition of ODC activity in the DRG appears unlikely since only high concentrations of vinblastine (0.5-1.0 mM) were able to inhibit ODC activity in vitro. We suggest vinca alkaloids inhibit ODC induction as a consequence of disrupting retrograde axonal transport. Interruption of this intracellular communication mechanism may be etiologically linked to the the distal axon degeneration which follows repetitive exposure to vinca alkaloids and other agents that induce toxic axonal neuropathy.
Soiefer
A I
AI
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, N.Y.
Moretto
A
A
Spencer
P S
PS
Sabri
M I
MI
D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000502:physiology*; D003714:Denervation; D004790:Enzyme Induction; D005727:Ganglia, Spinal / Q000187:drug effects / Q000201:enzymology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D065108:Ornithine Decarboxylase Inhibitors; D014748:Vinca Alkaloids / Q000494:pharmacology*
D065108:Ornithine Decarboxylase Inhibitors; D014748:Vinca Alkaloids; D009955:Ornithine Decarboxylase