Metabolism and inactivation of gastrin releasing peptide by endopeptidase-24.11 in the dog.
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.
Bunnett
N W
NW
Department of Surgery, University of California, San Francisco 94143.
Turner
A J
AJ
Debas
H T
HT
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001839:Bombesin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D015260:Neprilysin / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism
D001639:Bicarbonates; D005755:Gastrins; D010446:Peptide Fragments; D011506:Proteins; C040794:neuromedin C; D015260:Neprilysin; D001839:Bombesin