Metabolism of enkephalin in stomach wall of rats

Journal Article · Mon Jan 01 04:00:00 EST 1990 · American Journal of Physiology; (USA)

OSTI ID:7191456

Bunnett, N W; Walsh, J H; Debas, H T ^[1]

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1. Univ. of California, San Francisco (USA)

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.

• OSTI ID: 7191456
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 258; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CELL CONSTITUENTS
CELL MEMBRANES
DIGESTIVE SYSTEM
DRUGS
ENDORPHINS
ENKEPHALINS
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
GASTROINTESTINAL TRACT
HYDROGEN COMPOUNDS
HYDROLASES
ISOTOPE APPLICATIONS
MAMMALS
MEMBRANES
METABOLISM
MUSCLES
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HYDROLASES
PEPTIDES
POLYPEPTIDES
PROTEINS
RATS
RODENTS
STOMACH
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES