Dissociation of the inhibition of fast axonal transport by chlorimipramine from an effect on axonal microtubules.
The effect of in vitro exposure of bullfrog spinal nerves to 0.2 mM chlorimipramine on the density of axonal microtubules was studied in an attempt to clarify the mechanism by which chlorimipramine inhibits fast axonal transport. A 17-h exposure to chlorimipramine reduced the density of microtubules in unmyelinated axons by only 18%; this microtubular loss does not reach the upper limit of the range of microtubule reduction associated with inhibition of fast axonal transport. A 23-h exposure to chlorimipramine, which had decreased microtubular density in unmyelinated axons by 40% in a previous study, did not decrease microtubular density in myelinated axons in the present study. These results rule out microtubular destruction as the mechanism responsible for inhibition of fast orthograde axonal transport by chlorimipramine, and greatly reduce the likelihood that microtubular destruction plays a significant role in the inhibition of fast retrograde transport by chlorimipramine.
Lavoie
P A
PA
Département de pharmacologie, Faculté de médecine, Université de Montréal, Canada.
Filion
P R
PR
Pharand
M
M
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D001369:Axons / Q000145:classification / Q000187:drug effects / Q000378:metabolism; D002997:Clomipramine / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects*; D011892:Rana catesbeiana
D002997:Clomipramine