Effects of clonidine on lidocaine-induced inhibition of axonal transport in cultured mouse dorsal root ganglion neurones.
BACKGROUND
The alpha(2)-adrenoceptor agonist clonidine is used in combination with lidocaine for anaesthesia. Lidocaine inhibits axonal transport and neurite growth, whereas alpha(2)-adrenoceptor agonists have neurotrophic effects. Here we have investigated whether clonidine reduces lidocaine-induced inhibition of axonal transport in cultured mouse dorsal root ganglion neurones.


METHODS
Axonal transport of organelles and neurite growth were assessed by video microscopy in cells treated with clonidine and lidocaine for 1 h. Stable responses were achieved within this period.


RESULTS
Clonidine (10 and 100 microM) increased and lidocaine (10, 100 microM, and 1 mM) decreased axonal transport. The inhibitory effects of lidocaine were reduced by simultaneous treatment with clonidine. The actions of clonidine were antagonized by the alpha(2)-adrenoceptor antagonist yohimbine. Since clonidine was reported to block N-type channels, we further investigated the role of ion channels in the antagonistic action of clonidine on the lidocaine response. The action of lidocaine on axonal transport was not mimicked by the Na+ channel blocker tetrodotoxin and not blocked by the Na+ channel activator veratridine. The action of lidocaine was not blocked by the L-type Ca2+ channel blocker nifedipine, but was blocked by the N-type channel blocker omega-conotoxin MVIIA. These effects on axonal transport correlated with the effects on neurite growth.


CONCLUSIONS
Inhibition of axonal transport induced by lidocaine, which may be mediated by N-type channel activation, can be blocked by clonidine. Clonidine may alleviate the effects of lidocaine on neuronal dysfunction.
Hiruma
H
H
Department of Physiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara 228-8555, Japan. hiruma@med.kitasato-u.ac.jp
Shimizu
K
K
Takenami
T
T
Sugie
H
H
Kawakami
T
T
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D008012:Lidocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video; D009433:Neural Inhibition / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D015388:Organelles / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000779:Anesthetics, Local; D008012:Lidocaine; D003000:Clonidine