Substance P stimulates the release of Met5-enkephalin-Arg6-Phe7 and Met5-enkephalin from rat spinal cord.

Substance P (10(-6) M) injected in the fluid perfusing the subarachnoidal spaces of the spinal cord can release met5-enkephalin (YGGFM) and met5-enkephalin-Arg6-Phe7 (YGGFMRF) from spinal cord. This effect is Ca2+ dependent and can be blocked by the substance P antagonist, D-pro2, -D Trp7,9-substance P. The release of YGGFM and YGGFMRF was not observed when substance P was replaced by substance P1-9. These results suggest that substance P receptors are involved in triggering the release of enkephalins.