Inhibition of rapid axonal transport in vitro by the ionophores X-537 A and A 23187.
The effects of the ionophores X-537 A and A 23187 on axonal transport (AXT)' high energy phosphates, levels of Ca2+ and ultrastructure were investigated in frog sciatic nerves in vitro. X-537 A at 0.09 muM blocked AXT of [3H]labelled proteins by 50% as judged by ligature experiments while the levels of ATP and CrP remained unchanged. Pulse-label experiments showed that the amount of transported material decreased whereas the rate of AXT was only slightly retarded. Elevated extracellular levels of Ca2+ (5mM) potentiated the inhibitory effect of the ionophore. In contrast, ruthenium red counteracted the ionophore induced inhibition of AXT. A 23187 at 10 muM but not at 2 muM inhibition AXT but also reduced the ATP and CrP levels. In pulse-label experiments A 23187 displayed similar but less pronounced effects than X-537 A. Both ionophores increased the total calcium content of the nerve and appeared to decrease the amount of axonal mictotubles (MT). As X-537 is a very potent inhibitor of AXT it may prove a valuable tool in exploring the relations between AXT, Ca2+ and MT.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001370:Axonal Transport / Q000187:drug effects*; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D007700:Kinetics; D007832:Lasalocid / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011896:Rana temporaria; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
D000900:Anti-Bacterial Agents; D009419:Nerve Tissue Proteins; D010725:Phosphocreatine; D000001:Calcimycin; D000255:Adenosine Triphosphate; D002118:Calcium; D007832:Lasalocid