Inhibition of enkephalin-degrading aminopeptidase activity by certain peptides

Inhibition of a Membrane‐Bound Enkephalin‐Degrading Aminopeptidase by Bestatin Analogs

“…The purification of aminopeptidases from both membrane-bound and soluble fractions of brain tissues of various animals was reported together with some potent inhibitors of these enzymes (Hayashi and Oshima, 1977;Hayashi, 1978;Schnebli et al, 1979;Barclay and Phillipps, 1980;Hersh, 1981;Hersh and McKelvy, 1981;Wagner et al, 1981;Wagner and Dixon, 1981;Coletti-Previero et al, 1982;Hui et al, 1983;Shimamura et al, 1983). As reported previously, we purified a mernbranebound enkephalin-degrading aminopeptidase from monkey brain and found that amastatin and bestatin strongly inhibited it (Shimamura et al, 1983).…”

Substance P

“…To some extent these effects seems to be related to an opioid-like action, since naloxone neutralizes the substance P-analgesia (Stewart et al, 1976). The analgesic effects of substance P may also be explained by the inhibition of enkephalinases by substance P or by complex interactions involving the descending inhibitory serotonergic-substance P pathways (Barclay and Phillipps, 1980). Herein, the colocalisation of enkephalins with substance P may prove to be relevant (Ribeiro da Silva et al, 1992;Liu et al, 1996).…”

Angiotensin III: A Potent Inhibitor of Enkephalin‐Degrading Enzymes and an Analgesic Agent

“…In a search for inhibitors of enkephalin-degrading enzymes, it was found that some bioactive peptides acted as inhibitors against these enzymes (Barclay and Phillipps, 1980;Hudgin et al, 198 l), and angiotensin I inhibited the aminopeptidase activity in the brain (Hudgin et al, 1981;Shimamura et al, 1983). The present study is on the inhibitory activities of the angiotensins, bradykinins, and related peptides against enkephalin-degrading enzymes from the membranebound fraction of monkey brain or human CSF.…”

“…The differences between the above results may be due to the purity of these enzymes or to species selectivity. Substance P and somatostatin have also been reported to be competitive inhibitors of enkephalin-degrading aminopeptidase in the rat brain soluble fraction and were also shown to be potent analgesic agents by means of the tail flick test in rats, the hot plate test in mice, or both (Stewart et al, 1976;Frederickson et al, 1978;Malick and Goldstein, 1978;Rezek et al, 1978;Barclay and Phillipps, 1980). With regard to these phenomena, it was postulated that these substances may influence the degradation of endogenous opioid ligands.…”