The 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. GRP10 was metabolized in vitro by gastric endopeptidase‐24.11. The metabolites were purified by high‐pressure liquid chromatography and identified as (1‐8) GRP10 and (9‐10) GRP10 by amino acid analysis, indicating hydrolysis of the His8‐Leu9 bond. The intravenous administration of GRP10 to conscious dogs stimulated gastrin release, gastric acid secretion, pancreatic protein secretion and pancreatic bicarbonate secretion. Incubation of GRP10 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 GRP10.
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