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

Incubation of substance P in human plasma at 37°C resulted in rapid conversion to des (Arg¹Pro²) substance P (fragment 3-11) and to des (Arg¹-Pro²-Lys³-Pro⁴) 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.