Catabolism of gastrin releasing peptide and substance P by gastric membrane-bound peptidases.
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.
Bunnett
N W
NW
Kobayashi
R
R
Orloff
M S
MS
Reeve
J R
JR
Turner
A J
AJ
Walsh
J H
JH
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D019886:Gastrin-Releasing Peptide; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D006020:Glycopeptides / Q000494:pharmacology; D007700:Kinetics; D010447:Peptide Hydrolases / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D013270:Stomach / Q000201:enzymology*; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism*; D013379:Substrate Specificity; D013552:Swine
D005768:Gastrointestinal Hormones; D006020:Glycopeptides; D010455:Peptides; D011480:Protease Inhibitors; D013373:Substance P; D019886:Gastrin-Releasing Peptide; D010447:Peptide Hydrolases; C008890:phosphoramidon