抄録
Whereas the central nervous system usually cannot regenerate, axons within the peripheral nervous system regenerate spontaneously and rapidly after injury. To study molecular mechanisms of peripheral nerve regeneration, we established the sciatic nerve transection–regeneration model by using a combination of tabulation and osmotic mini–pump to deliver drugs at a constant rate for at least 4 weeks and have recently demonstrated that endothelin (ET)–1 was involved in the nerve regeneration. In the present study, to clarify which receptors of ET–1 mediated its action, we examined the effect of ETAR and ETBR antagonists on the functional recovery. Mice started to resume mechanical responses of their hind paws 5 weeks after the sciatic nerve transection and returned to the level before operation by 7 weeks. Time course of the functional recovery is well correlated with that of nerve regeneration assessed by elongation of axons expressing yellow fluorescent protein and application of fluoro–ruby, a fluorescent retrograde tracer, to the distal stump of the transected nerve. The ETBR antagonist, but not ETAR antagonist, delayed the functional recovery in the model mice. Taken together with ETBR expression in Schwann cells, these results demonstrate that ET–1 is involved in peripheral nerve regeneration via ETBR.
