Degradation of endogenous heptadecapeptide gastrin by endopeptidase 24.11 in the pig.
Hydrolysis of heptadecapeptide gastrin (G-17) by endopeptidase 24.11 (EC 3.4.24.11) was studied in vivo and in vitro in the pig. Ion exchange chromatography and radioimmunoassay with three region-specific antisera were used to identify the products of porcine G-17 degradation. Incubation of antral extracts with pure endopeptidase 24.11 resulted in a substantial loss of intact G-17: 80% C-terminal immunoreactivity was lost in 60 min. This hydrolysis was completely inhibited by phosphoramidon, which is a specific inhibitor of endopeptidase 24.11. In antral extracts G-17 accounted for greater than 95% of total C-terminal immunoreactivity, compared with less than 60% C-terminal immunoreactivity in the gastric venous outflow; shorter C-terminal forms comprised the major part of the remaining immunoreactivity. After infusion of phosphoramidon, the concentration of intact G-17 was increased, and there was a corresponding reduction in the concentration of other C-terminal immunoreactive fragments. We conclude that endopeptidase 24.11 degrades G-17 in vitro and in vivo and may be responsible for the generation of C-terminal fragments from G-17 after secretion from the porcine antral mucosa.
Power
D M
DM
Bunnett
N
N
Turner
A J
AJ
Dimaline
R
R
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D005755:Gastrins / Q000378:metabolism*; D006020:Glycopeptides / Q000494:pharmacology; D006868:Hydrolysis; D008297:Male; D015260:Neprilysin; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism; D011480:Protease Inhibitors; D011706:Pyloric Antrum / Q000032:analysis / Q000098:blood supply; D013552:Swine; D014020:Tissue Extracts / Q000378:metabolism; D014680:Veins
D005755:Gastrins; D006020:Glycopeptides; D010446:Peptide Fragments; D011480:Protease Inhibitors; D014020:Tissue Extracts; C013550:gastrin 17; D010450:Endopeptidases; D015260:Neprilysin; C008890:phosphoramidon