Inhibition of peptidases potentiates enkephalin-stimulated contraction of gastric muscle cells

D. Menozzi, Z. F. Gu, P. N. Maton, N. W. Bunnett

Research output: Contribution to journalArticlepeer-review


Cell surface peptidases degrade enkephalins and thereby restrict the number of molecules available to activate receptors. The effects of peptidase inhibitors on degradation of enkephalins and on enkephalin-stimulated contraction of gastric smooth muscle cells were examined. Muscle cells dispersed from the guinea pig stomach degraded [Tyr1-3H][Leu5]enkephalin (41.6 ± 9.0% degradation at 60 min incubation, mean ± SD, n = 4 animals). Amastatin (10 μM, an aminopeptidase inhibitor) inhibited degradation by 72.1 ± 1.5%. The residual peptidase activity was inhibited by phosphoramidon (1 μM, an endopeptidase EC inhibitor) by 58.0 ± 11.0%. [Tyr1-125I][Met5]enkephalin was similarly degraded. Phosphoramidon (1 μM) inhibited the degradation of the aminopeptidase-resistant peptide [Tyr1-3H][D-Ala2][Leu5] enkephalin by >95%. [Met5]enkephalin, incubated with cells for 30 s, stimulated contraction [50% maximal contraction (EC50) 120 ± 50 nM, n = 6]. Pretreatment of cells with phosphoramidon alone, amastatin alone, or phosphoramidon plus amastatin, caused 20-fold (EC50 6.5 ± 1.1 nM), 2-fold (EC50 63 ± 23 nM), and 100-fold (EC50 1.1 ± 0.3 nM) increase in potency of [Met5]enkephalin, respectively. The results show that endopeptidase EC and aminopeptidases contribute to degradation of enkephalins by gastric muscle cells. The rapidity and magnitude of the potentiating effects of the inhibitors on enkephalin-stimulated contraction suggest a close physical relationship between the peptidases and the enkephalin receptors.

Original languageEnglish (US)
Pages (from-to)G476-G484
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number3 24-3
StatePublished - 1991


  • Aminopeptidase
  • Enkephalinase
  • Neuropeptidase
  • Peptide degradation

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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