Inhibition of cell division and the development of denervation hypersensitivity in skeletal muscle.

1. It was found that in 3 day denervated soleus and EDL muscles nuclear division takes place. This can be stopped by administration of either 5-fluoro-uracil or vincristine. 2. The increased sensitivity to acetylcholine following denervation developed at a time when rapid cell division takes place. Both 5-fluoro-uracil and vincristine prevent the development of denervation hypersensitivity both in soleus and EDL muscles. 3. Muscle injury causes some cell division locally, but some phagocytic cells that infiltrate the damaged muscle appear to be blood-borne as their appearance within the muscle is not entirely prevented by either 5-fluoro-uracil or vincristine. Correspondingly the development of increased sensitivity that follows muscle injury is only partly prevented by administration of cytotoxic drugs. 4. It is suggested that the presence of dividing cells is causally related to the development of denervation hypersensitivity.