Metabolism and Inactivation of Gastrin Releasing Peptide by ENDOPEPTIDASE‐24.11 in the Dog

Abstract

SUMMARYThe purpose of this investigation was to examine the metabolism and inactivation of gastrin releasing peptide 10 (GRP10) by endopeptidase-24. 11 prepared from the stomach wall. GRP1O was metabolized in vitro by gastric endopeptidase-24. 11. The metabolites were purified by high-pressure liquid chromatography and identified as (1-8) GRP1O and (9-10) GRP1O by amino acid analysis, indicating hydrolysis of the His8-Leu8 bond. The intravenous administration of GRP10 to conscious dogs stimulated gastrin release, gastric acid secretion, pancreatic protein secretion and pancreatic bicarbonate secretion. Incubation of GRPIO with endopeptidase-24. 11 significantly diminished the biological activity of the digests compared to control digests containing heat-inactivated enzyme. This effect was abolished by the enzyme inhibitor phosphoramidon. It is concluded that endopeptidase-24. 11 from the stomach metabolizes and inactivates GRPIO.

CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung.

“…In earlier studies, a phosphoramidon inhibitable membrane bound peptidase from gastric tissue with characteristics of NEP was reported to cleave a dipeptide from neuromedin C [GRP-(18-27)] after prolonged incubation (42,43). We find that CD10/NEP rapidly inactivates each of the BLP family Cell Biology: Shipp et al…”

Neutral endopeptidase (EC 3.4.24.11) modulates the contractile effects of neuropeptides on muscle cells from the guinea‐pig stomach

“…NEP degrades neuropeptides by hydrolysing peptide bonds on the amino-terminal side of hydrophobic residues such as phenylalanine, leucine, tyrosine and tryptophan. Kinetically favourable substrates include substance P, enkephalins, gastrin-releasing peptide-10 (GRP-10) (Matsas, Fulcher, Kenny & Turner, 1983;Matsas, Kenny & Turner, 1984;Bunnett, Kobayashi, Orloff, Reeve, Turner & Walsh, 1985;Bunnett et al 1988a;Bunnett, Turner & Debas, 1989) and somatostatin-14 (Sakurada, Yokosawa & Ishii, 1990).…”