On the degradation of enkephalins and endorphins by rat and mouse brain extracts

Action of proteolytic enzymes on lipotropins and endorphins: Biosynthesis, biotransformation and fate

“…However, after 30 min, 60 min and 180 min of incubation Marks et al, 1978;Marks, 1978) all amino acid residues were detected in approximately equal amounts, with some preference for tyrosin, methionine, glutamine and leucine (for the primary structure of fl-endorphin see Table 2). Using a similar approach Patthy et al (1977) also observed a time dependent release of all the constituent amino acids, proportionally to the data reported by Marks et al (1977) except for methionine which was considerably lower in the experiment of Patthy and co-workers and phenylalanine and lysine which were released more rapidly. These studies indicated: (1) that initially a limited number of peptide bonds are cleaved and (2) that multiple types of enzyme activities cleaving the fl-endorphin sequence at different sites are involved in the degradation.…”

“…This process has mainly been investigated by following the release of amino acids during exposure of fl-endorphin to soluble fractions of brain tissue. Marks et al, (1977) observed that after 5 min of incubation at pH 7.6 3 to 7~o of several amino acid residues from different positions of the fl-endorphin sequence appeared, while other amino acids were absent. However, after 30 min, 60 min and 180 min of incubation Marks et al, 1978;Marks, 1978) all amino acid residues were detected in approximately equal amounts, with some preference for tyrosin, methionine, glutamine and leucine (for the primary structure of fl-endorphin see Table 2).…”

Neuronal localization of the neutral endopeptidase ‘enkephalinase’ in rat brain revealed by lesions and autoradiography.

“…In accordance with their well-admitted neurotransmitter role in the central nervous system (Hughes, 1983), the action of the opioid peptides Leu or Met-enkephalin is switched off in vivo by several peptidases: aminopeptidase(s) (Hambrook et al, 1976;Marks et al, 1977), dipeptidylaminopeptidase (Gorenstein and Snyder, 1979) and the neutral endopeptidase (EC 3.4.24.11) (Kerr and Kenny, 1974) also designated enkephalinase (Malfroy et al, 1978).…”

Autoradiographic comparison of the distribution of the neutral endopeptidase "enkephalinase" and of mu and delta opioid receptors in rat brain.

“…The endogenous opioid peptide enkephalins are chiefly and rapidly metabolized in the brain (1) by both an aminopeptidase activity (2,3) and enkephalinase (4), a membrane-bound enzyme identical to the neutral metalloendopeptidase EC 3.4.24.11 (5). The physiological relevance of brain enkephalinase is supported by the naxolone-reversible decrease in the responsiveness to nociceptive stimuli -elicited by intracerebral administration of highly potent enkephalinase inhibitors such as thiorphan {N-[(2RS)-2-mercaptomethyl-1-oxo-3-phenylpropyl]glycine} (6) or kelatorphan {N-[(2R)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]-L-alanine} (7), a compound belonging to a new series of bidentate inhibitors.…”