Catabolism of gastrin releasing peptide and substance P by gastric membrane-bound peptidases

N. W. Bunnett, R. Kobayashi, M. S. Orloff, J. R. Reeve, A. J. Turner, J. H. Walsh

Research output: Contribution to journalArticlepeer-review

Abstract

The catabolism of two gastric neuropeptides, the C-terminal decapeptide of gastrin releasing peptide-27 (GRP10) and substance P (SP), by membrane-bound peptidases of the porcine gastric corpus and by porcine endopeptidase-24.11 ("enkephalinase") has been investigated. GRP10 was catabolized by gastric muscle peptidases (specific activity 1.8 nmol min-1 mg-1 protein) by hydrolysis of the His8-Leu9 bond and catabolism was inhibited by phosphoramidon (I50 approx. 10-8 M), a specific inhibitor of endopeptidase-24.11. The same bond in GRP10 was cleaved by purified endopeptidase-24.11, and hydrolysis was equally sensitive to inhibition by phosphoramidon. SP was catabolized by gastric muscle peptidases (specific activity 1.7 nmol min-1 mg-1 protein) by hydrolysis of the Gln6-Phe7, Phe7-Phe8 and Gly9-Leu10 bonds, which is identical to the cleavage of SP by purified endopeptidase-24.11. The C-terminal cleavage of GRP10 and SP would inactivate the peptides. It is concluded that a membrane-bound peptidase in the stomach wall catabolizes and inactivates GRP10 and SP and that, in its specificity and sensitivity to phosphoramidon, this peptidase resembles endopeptidase-24.11.

Original languageEnglish (US)
Pages (from-to)277-283
Number of pages7
JournalPeptides
Volume6
Issue number2
DOIs
StatePublished - 1985

Keywords

  • Angiotensin converting enzyme
  • Captopril
  • Endopeptidase-24.11
  • Gastrin releasing peptide
  • Phosphoramidon
  • Substance P

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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