Metabolism of substance P in human plasma and in the rat circulation

Abstract Incubation of substance P in human plasma at 37°C resulted in rapid conversion to des (Arg 1 Pro 2 ) substance P (fragment 3–11) and to des (Arg 1 -Pro 2 -Lys 3 -Pro 4 ) substance P (fragment 5–11). The metabolites were purified by high-performance liquid chromatography and identified by sequence analysis. These data are consistent with the hypothesis that substance P is metabolized by enzyme(s) with the specifity of dipeptidyl aminopeptidase IV (EC 3.1.14.5). Analysis by high-performance liquid chromatography of plasma extracts following intravenous infusion of substance P (300–350 nmoles) into anaesthetized rats showed that the peptide was cleared from the circulation within 1–2 minutes. No circulating metabolites could be identified.