A correlation between the effects of anti-mitotic drugs on microtubule assembly in vitro and the inhibition of axonal transport in noradrenergic neurones.
1. Podophyllotoxin, colchicine and griseofulvin inhibit the intra-axonal movement of noradrenaline storage vesicles in cat hypogastric nerve/inferior mesenteric ganglion preparations maintained in vitro, cause the disappearance of axonal microtubules and inhibit the assembly of microtubules from tubulin in vitro. The order of potency of the three effects is podophyllotoxin greater than colchicine greater than griseofulvin. 2. Lumicolchicine is without effect on the three parameters and does not interfere with the binding of tritiated colchicine to tubulin. 3. Podophyllotoxin causes a more rapid loss of microtubules from axons than the same concentration of colchicine. 4. The experiments provide strong evidence that microtubules are components of the system responsible for the intra-axonal migration of noradrenaline storage vesicles.
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002415:Cats; D003078:Colchicine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006118:Griseofulvin / Q000494:pharmacology; D007001:Hypogastric Plexus / Q000187:drug effects; D066298:In Vitro Techniques; D008870:Microtubules / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D011034:Podophyllotoxin / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
D014404:Tubulin; D006118:Griseofulvin; D011034:Podophyllotoxin; D003078:Colchicine; D009638:Norepinephrine