Inactivation of substance P and its C-terminal fragments in rat plasma and its inhibition by Captopril

Abstract

The metabolic degradation of substance P(SP), some of its C-terminal fragments, and some analogues by rat plasma has been evaluated from the disappearance of the biological activities of these peptides on the guinea pig isolated ileum. The experiments were performed by dissolving each peptide in saline and by adding 20% (v/v) of rat plasma for incubation at 37 °C for various periods of time.It was found that SP and octapeptide 4–11 are inactivated quite rapidly and at approximately the same rate whereas SP-free acid, heptapeptide 5–11, hexapeptide 6–11, and [D-Trp8]-SP are inactivated more slowly. The replacement of Phe7 by D-Trp does not protect the undecapeptide SP from inactivation.The degradation of SP and of all the C-terminal fragments was completely blocked by Captopril at a concentration of 10 μg/mL of plasma. Under these conditions, Captopril also slightly reduced the rate of inactivation of bradykinin and of SP-free acid.These results were interpreted as indicative of the presence in rat plasma of an endopeptidase that hydrolyses a peptide bond in the C-terminal pentapeptide sequence of SP. This endopeptidase is completely inactivated by Captopril, which thus appears to be not as specific for the angiotensin-converting enzyme as it was thought to be.