Conversion of substance P to C-terminal fragments in human plasma

J. Michael Conlon, Lindy Sheehan

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58 Citations (Scopus)

Abstract

Substance P is rapidly converted by enzyme(s) in human plasma to des-[Arg1Pro2]-substance P (fragment 3-11) and to des-[Arg1Pro2Lys3Pro4]-substance P (fragment 5-11). These metabolites were isolated by HPLC and partially sequenced. No evidence was obtained for deamidation of substance P in plasma or for the formation of the N-terminal tetrapeptide [Arg-Pro-Lys-Pro]. The data suggest that substance P is metabolized in human plasma by an enzyme with the specificity of dipeptidyl-aminopeptidase IV. Consistent with this hypothesis, the rate of degradation of substance P measured with an antibody directed against the N-terminal region is 2-3-fold greater than measured with a C-terminally directed antibody. The degrading activity of plasma was purified 522-fold and was eluted from a gel filtration column in the molecular weight zone 150 000-170 000 and from a chromatofocusing column in the pH range 4.5 to 5.5.

Original languageEnglish
Pages (from-to)335-345
Number of pages11
JournalRegulatory Peptides
Volume7
Issue number4
DOIs
Publication statusPublished (in print/issue) - Dec 1983

Keywords

  • chromatofocusing
  • dipeptidylaminopeptidase IV
  • HPLC
  • metabolite
  • peptidase
  • radioimmunoassay

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