Metabolism of enkephalin in stomach wall of rats.
Peptidases degrade neuropeptides and thereby limit the duration and extent of their influence. This investigation examined the importance of peptidases in the degradation of the neuropeptide enkephalin in the stomach wall of the rat. Metabolism of [Leu5]- and [D-Ala2][Leu5]enkephalin by gastric membranes was examined in vitro. Degradation of [Tyr1-3H][Leu5]enkephalin was studied in the gastric submucosa of anesthetized and conscious rats in vivo by using a catheter to deliver peptide to tissues and implanted dialysis fibers to collect the metabolites. Specific inhibitors were used to assess the contribution of particular enzymes. [Leu5]- and [Tyr1-3H][Leu5]enkephalin were metabolized by membranes and in the stomach wall by hydrolysis of the Tyr1-Gly2 bond. Degradation was inhibited by the aminopeptidase inhibitor amastatin (10(-5) M in vitro, 10 nmol in vivo). Inhibitors of endopeptidase-24.11 (phosphoramidon) and angiotensin-converting enzyme (captopril) did not inhibit degradation. Metabolism of the aminopeptidase-resistant analogue [D-Ala2][Leu5]enkephalin by membranes was unaffected by amastatin and weakly inhibited by phosphoramidon affected by amastatin and weakly inhibited by phosphoramidon and captopril. A carboxypeptidase removed the COOH-terminal leucine residue and made a substantial contribution to degradation of both peptides by gastric membranes.
Bunnett
N W
NW
Department of Surgery, University of California, San Francisco 94143.
Walsh
J H
JH
Debas
H T
HT
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D004745:Enkephalins / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014316:Tritium
D004745:Enkephalins; D011480:Protease Inhibitors; D014316:Tritium; D010447:Peptide Hydrolases