The effect of peptidase inhibitors on the release of Met5-Enk-Arg6-Phe7 (YGGFMRF) and Met5-enkephalin (YGGFM) from spinal cord induced by substance P in vivo.

Using a preparation for the perfusion of the subarachnoidal spaces of the spinal cord of rats it was found that substance P can stimulate the release of YGGFMRF and YGGFM. We have studied the effect of several peptidase inhibitors (captopril, bestatin, thiorphan) on the recovery of YGGFMRF and YGGFM released from spinal cord by substance P. The recovery of released YGGFMRF was increased by adding captopril to the perfusion medium. A combination of captopril and bestatin in the perfusion medium further increases this YGGFMRF recovery. Intrathecal injection of captopril and bestatin also potentiated the analgesic effect of YGGFMRF and electroacupuncture. These results suggest that substance P may act as a "releaser" of enkephalins in spinal cord and that the dipeptidyl carboxypeptidase and aminopeptidase may be important in the degradation of YGGFMRF in vivo.