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Evidence that the agonist action of dynorphin A(1–8) in the guinea‐pig myenteric‐plexus may be mediated partly through conversion to [Leu 5 ]enkephalin
Author(s) -
Dixon Diane M.,
Traynor J.R.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14139.x
Subject(s) - myenteric plexus , agonist , enkephalin , guinea pig , endocrinology , leu enkephalin , dynorphin , chemistry , medicine , pharmacology , biology , opioid peptide , biochemistry , opioid , receptor , immunohistochemistry
1 The agonist action of the opioid peptide dynorphin A(1–8) on the myenteric plexus‐longitudinal muscle of the guinea‐pig ileum has been characterized. 2 The endogenous opioid peptide dynorphin A(1–8) was rapidly degraded by slices of myenteric plexus‐longitudinal muscle of the guinea‐pig ileum. 3 A product of the degradation was the δ‐receptor preferring [Leu 5 ]enkephalin. Levels of [Leu 5 ]enkephalin were markedly increased in the presence of the peptidase inhibitors bestatin, thiorphan and captopril. 4 In the myenteric plexus dynorphin A(1–8) acted as a κ‐receptor agonist. In the presence of bestatin, thiorphan and captopril a μ‐receptor agonist effect was observed. This μ‐agonist action was lost in the presence of N‐[1‐(RS)‐carboxy‐2‐phenylethyl]Ala‐Ala‐Phe‐ p ‐aminobenzoate, an inhibitor of the endopeptidase enzyme EC 3.4.24.15. 5 The results suggest that formation of [Leu 5 ]enkephalin from dynorphin A(1–8) may be an important conversion process. The enzyme responsible may be the Zn 2+ ‐metalloendopeptidase, EC 3.4.24.15.