IS SUBSTANCE-P RELEASED FROM SLICES OF THE RAT SPINAL-CORD INACTIVATED BY PEPTIDASE(S) DISTINCT FROM BOTH ENKEPHALINASE AND ANGIOTENSIN-CONVERTING ENZYME

Studies on the effects of peptidase inhibitors on substance P-like immunoreactive material (SPLI) released by K+ -induced depolarization from slices of the rat spinal cord showed that bacitracin was the most potent agent to protect SPLI from degradation. Captopril and thiorphan which inhibit, respectively, angiotensin I converting enzyme and endopeptidase-24.11 also protected SPLI from degradation. However other inhibitors of these two enzymes, kelatorphan for endopeptidase-24.11 and enalaprilat for angiotensin I converting enzyme were essentially inactive, indicating that both enzymes are probably not involved in the degradation of endogenous substance P. Instead, the non-additive protecting effect of bacitracin, captopril and thiorphan might be due to the blockade of some 'bacitracin-sensitive enzyme' playing a key role in the catabolism of SP within the rat spinal cord.