PEPTIDASE INHIBITORS IMPROVE RECOVERY OF SUBSTANCE-P AND CALCITONIN-GENE-RELATED PEPTIDE RELEASE FROM RAT SPINAL-CORD SLICES

The purpose of present study was to determine whether peptidase activi ty affects the release of substance P (SP) and calcitonin gene-related peptide (CGRP) from spinal cord slices. When slices were exposed to v arious inhibitors of endopeptidase 24.11, the resting and capsaicin-st imulated release of SP were less than 0.04% and 0.20% total content pe r minute, respectively. Resting CGRP release was approximately 0.10% a nd stimulated release was 0.40%. The combination of 20 mu M bacitracin , 100 mu M phenylalanylalanine (Phe-Ala), and 50 mu M p-chloromercurip henylsulfonic acid (PCMS) significantly increased both resting and sti mulated release of SP and CGRP at least two- or threefold. Doubling th e concentration of PCMS and Phe-Ala did not further improve peptide re lease. These results demonstrate that recovery of peptides released fr om spinal cord slices is dependent in part on activity of multiple pep tidases in the tissues.