SUBSTANCE-P - INVITRO INACTIVATION BY RAT-BRAIN FRACTIONS AND HUMAN-PLASMA

The in vitro degradation of substance P (SP) by rat brain fractions and human plasma was studied by means of polyacrylamide gel electrophoresis and 3H-[Nle]11SP. Substance P was degraded by neutral metalloendopeptidase systems of the crude synaptosomal fraction and plasma with Km values of 3.6 × 10-5 and 8 × 10-6 M, respectively. The peptide was also degraded by other subcellular brain fractions. The degradation rates corresponded with the biological inactivation as assayed on guinea pig ileum. The basic N-terminal sequence of the peptide was found to be important for this inactivation. No specific uptake of the peptide in the synaptosomal brain fraction could be observed. It is concluded that in vivo substance P is degraded with first order dependence and that this proteolytic breakdown is responsible for the termination of the biological activity of substance P as a putative neurotransmitter or neuromodulator. © 1979.