Inhibition of enkepha,in metabolism by, and antinociceptive activity of, bestatin, an aminopeptidase inhibitor

Chaillet, Pierre; Marcais-Collado, H.; Costentin, Jean; Yi, Chin-Cheng; Baume, Sophie de la; Schwartz, Jean‐Charles

doi:10.1016/0014-2999(83)90181-4

Cited by 135 publications

(29 citation statements)

References 31 publications

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“…1). It has been shown previously that the inhibition of enzymatic degradation of Met-enk results in the potentiation of the effects of Met-enk administered exogenously (17,23). Accordingly, the present results suggest that the dose of i.c.v.…”

Section: Discussionsupporting

confidence: 75%

Effects of a Mixture of Peptidase Inhibitors (Amastatin, Captopril and Phosphoramidon) on Met-Enkephalin-, β-Endorphin-, Dynorphin-(l-13)- and Electroacupuncture-Induced Antinociception in Rats

Kishioka¹,

Miyamoto²,

Fukunaga³

et al. 1994

Japanese Journal of Pharmacology

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ABSTRACT-The effects of a mixture of three peptidase inhibitors (PIs), amastatin, captopril and phosphoramidon, on methionine-enkephalin (Met-enk)-, j3-endorphin (p-end)-, dynorphin-(1 13) (Dyn) and electroacupuncture (EA)-induced antinociception were compared in rats. EA was performed by passing electric pulses (3 Hz, 0.1-msec duration, for 45 min) through acupuncture needles inserted into the Hoku point. The antinociceptive effect was estimated by the hind paw pressure test. The antinociceptive effects of Met-enk and p-end injected i.c.v. or Lt. and of Dyn injected i.t. were clearly potentiated by the PIs pretreated by the same administration routes as used for the injection of opioid peptides. The antinocicep tive effects of Met-enk, n-end and Dyn injected i.c.v. were also potentiated significantly by i.t.-PIs. PIs in jected into the periaqueductal gray (PAG) potentiated EA antinociception. However, the EA effect was not affected by i.t.-PIs and was rather attenuated by i.c.v.-PIs. These results suggest that: i) Met-enk hydro lyzing enzymes are involved in the degradation of not only Met-enk but also p-end and Dyn in the rat central nervous system; ii) Met-enk and n-end act on both supraspinal and spinal sites, while Dyn acts only on the spinal site; iii) EA antinociception is mediated by supraspinal Met-enk and/or n-end; and iv) an anti-opiate peptide system may be activated by EA stimulation, being susceptible to Met-enk hydrolyzing enzymes.

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Section: Discussionsupporting

confidence: 75%

Effects of a Mixture of Peptidase Inhibitors (Amastatin, Captopril and Phosphoramidon) on Met-Enkephalin-, β-Endorphin-, Dynorphin-(l-13)- and Electroacupuncture-Induced Antinociception in Rats

Kishioka¹,

Miyamoto²,

Fukunaga³

et al. 1994

Japanese Journal of Pharmacology

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“…Indeed, effects of the natural opioid, enkephalin, in guinea-pig ileum, rat and mouse vas deferens and in rat brain were potentiated by aminopeptidase inhibition (Chaillet et al, 1983;Cohen et al, 1983;McKnight et al, 1983 Several factors may contribute to the lack of potentiation of VIP responses in the presence of these peptidase inhibitors. It may be that enzymes which degrade VIP were inaccessible to these agents although this seems unlikely for leupeptin (see above).…”

Section: Discussionmentioning

confidence: 99%

Relaxation of cat tracheobronchial and pulmonary arterial smooth muscle by vasoactive intestinal peptide: lack of influence by peptidase inhibitors

Altiere

Diamond

1984

British J Pharmacology

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1Vasoactive intestinal peptide (VIP) caused concentration-dependent relaxation in precontracted segments of trachea, hilar bronchus, intrapulmonary bronchus and intrapulmonary artery (IPA) isolated from cat lungs. 2 VIP-induced relaxation responses were abolished by preincubation of tissues with the proteolytic enzyme, a-chymotrypsin (2 units ml-). At the concentration employed, a-chymotrypsin treatment did not adversely affect tissue viability as isoprenaline and bethanechol continued to relax airways and IPA, respectively. 3 Aprotinin prevented enzymatic degradation of VIP by ax-chymotrypsin as demonstrated by the ability of VIP to relax tissues incubated with both the peptidase inhibitor and a-chymotrypsin. 4 A spectrum of peptidase inhibitors, including aprotinin, leupeptin, bestatin, bacitracin, jphenylpropionic acid and captopril, individually or in combination, did not augment the relaxant effects of VIP in isolated pulmonary tissues. 5These results suggest that local enzymatic degradation may not be a primary route for inactivation of VIP in cat isolated airways and IPA. If VIP acts as a neurotransmitter in these tissues, a mechanism other than enzymatic proteolysis may be responsible for terminating its action.

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“…This approach obviously requires a knowledge of the metabolic pathways of endogenous OPs. Endogenous enkephalins [Tyr-Gly-Gly-Phe-Met (YGGFM) and Tyr-GlyGly-Phe-Leu (YGGFL)] are degraded through (i) cleavage of the Tyr-Gly bond at residues 1 and 2 by a bestatin-sensitive aminopeptidase activity (14,15) (15,25) or in vivo (26,27), and its degradation is prevented by bestatin (15).…”

mentioning

confidence: 99%

Steady-state level and turnover rate of the tripeptide Tyr-Gly-Gly as indexes of striatal enkephalin release in vivo and their reduction during pentobarbital anesthesia.

Llorens-Cortes¹,

Gros²,

Schwartz³

1986

Proc. Natl. Acad. Sci. U.S.A.

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Communicated by E. Costa, April 7, 1986 ABSTRACT Tyr-Gly-Gly (YGG) was recently shown to be an extraneuronal metabolite of opioid peptides derived from proenkephalin A, formed in brain by the action of "enkephalinase" (membrane metalloendopeptidase, EC 3.4.24.11) and degraded by aminopeptidases. The dynamic state of YGG in mouse striatum was studied by evaluating the changes in its level elicited by inhibitors of these peptidases. Inhibition of YGG synthesis by Thiorphan or acetorphan reduced YGG levels with a til2 (mean ± SEM) of 12 ± 2 min, indicating an apparent turnover rate (mean ± SEM) of 18 ± 2 pmol/mg of protein per hr. An apparent turnover rate of 18 ± 2 pmol/mg of protein per hr was derived from the rate of YGG accumulation elicited by the aminopeptidase inhibitor bestatin. In addition, accumulation of Tyr-Gly-Gly-Phe-Met (YGGFM) in an extrasynaptosomal fraction after blockade ofits degradation by Thiorphan and bestatin occurred at a rate of 18 ± 3 pmol/mg of protein per hr, which is likely to reflect the rate of enkephalin release in vivo. Hence, the three series of data suggest that striatal enkephalins rapidly turn over-e.g., with

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Inhibition of enkepha,in metabolism by, and antinociceptive activity of, bestatin, an aminopeptidase inhibitor

Cited by 135 publications

References 31 publications

Effects of a Mixture of Peptidase Inhibitors (Amastatin, Captopril and Phosphoramidon) on Met-Enkephalin-, β-Endorphin-, Dynorphin-(l-13)- and Electroacupuncture-Induced Antinociception in Rats

Effects of a Mixture of Peptidase Inhibitors (Amastatin, Captopril and Phosphoramidon) on Met-Enkephalin-, β-Endorphin-, Dynorphin-(l-13)- and Electroacupuncture-Induced Antinociception in Rats

Relaxation of cat tracheobronchial and pulmonary arterial smooth muscle by vasoactive intestinal peptide: lack of influence by peptidase inhibitors

Steady-state level and turnover rate of the tripeptide Tyr-Gly-Gly as indexes of striatal enkephalin release in vivo and their reduction during pentobarbital anesthesia.

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