Degradation of cholecystokinin-like peptides by a crude rat brain synaptosomal fraction: A study by high pressure liquid chromatography

Deschodt-Lanckman, M; Bui, Ngoc Diem; Noyer, Michel; Christophe, Jean

doi:10.1016/0167-0115(81)90062-8

Cited by 81 publications

(13 citation statements)

References 41 publications

(39 reference statements)

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“…Cholecystokinin octapeptide (CCK-8) and Phe-Met-Arg Phe (FMRF) amide were shown to be released by (3-end (33) and morphine (34), respectively; and the regional dis tribution of these anti-opiate peptides in the brain was in dicated to be different from that of Met-enk (35,36). It was reported that CCK-8 was inactivated exclusively by aminopeptidase and enkephalinase (37), and the degrada tion of CCK-8 was reduced by bacitracin (38,39) and bestatin + phosphoramidon (40). The release of the C-ter minal phenylalanylamide of FMRF amide was induced by enkephalinase, and this hydrolysis was completely inhibit ed by phosphoramidon (40).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…Several studies have shown that ill-characterized acidic (13,14) or neutral aminopeptidases (13), enkephalinase (EC 3.4.24.11) (15)(16)(17), a thiol-endopeptidase (18) or a metallo-endopeptidase (19) may participate in the hydrolysis of exogenous by cerebral membranes, with cleavages occurring at various peptide bonds within the molecule. However, numerous peptidases capable of hydrolyzing neuropeptides are present in cerebral membranes, and metabolic pathways of exogenous neuropeptides may not reliably reflect those responsible for endogenous neuropeptide inactivation, as illustrated in the case of enkephalins' (1)(2)(3)(4)(5).…”

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confidence: 99%

A serine peptidase responsible for the inactivation of endogenous cholecystokinin in brain.

Rose

Camus

Schwartz

1988

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

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“…Both chelation of ions and blocking of sulfhydryl groups could inactivate enzymes involved in the biosynthesis and/or degradation of CCK and, thus, explain otir data. Recently, a CCK-8 and CCK-4 degrading enzyme was detected in both the cytosol and the synaptic membranes of brain tissue (33). Moreover, in vitro experiments showed that the degradation of CCK-8 and CCK-4 could be markedly inhibited by both chelating and sulfhydryl-blocking agents, suggesting that their degradation required the presence of a metal ion probably linked to a thiol group (33).…”

Section: Resultsmentioning

confidence: 96%

“…Recently, a CCK-8 and CCK-4 degrading enzyme was detected in both the cytosol and the synaptic membranes of brain tissue (33). Moreover, in vitro experiments showed that the degradation of CCK-8 and CCK-4 could be markedly inhibited by both chelating and sulfhydryl-blocking agents, suggesting that their degradation required the presence of a metal ion probably linked to a thiol group (33). Our results could be explained by reversible inactivation of such a CCK degrading enzyme.…”

Section: Resultsmentioning

confidence: 99%

“…The COOH-terminal octapeptide of 'CCK (CCK-8) appears to be a putative transmitter (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) with an excitatory effect on hippocampal pyramidal cells (31,32). Moreover, in vitro studies have indicated that a CCK-8 degrading enzyme is likely to be a metalloenzyme (33). These observations indicate a functional significance of the close relationship between heavy metals and CCK in the rat hippocampus.…”

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confidence: 84%

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Modulation of cholecystokinin concentrations in the rat hippocampus by chelation of heavy metals.

Stengaard‐Pedersen¹,

Larsson²,

Fredens³

et al. 1984

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

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Previously, we have reported that enkephalins, cholecystokinin, and heavy metals show roughly parallel distributional patterns in the hippocampus. A substantial body of evidence indicates that cholecystokinin-octapeptide (CCK-8) and enkephalins act as neurotransmnitters. A CCK-8 degrading enzyme was recently detected in brain synaptosomes. Its activity depended on free thiol groups and the presence of a heavy metal. Since the heavy metal-containing neuropil is closely related to CCK-immunoreactive nerve terminals, we have investigated the effect of metal chelation on CCK conmponents in the rat hippocampus. In vivo treatment of rats with a single dose of the chelating agent diethyldithiocarbamate caused a reversible chelation of heavy metals in the hippocampus. This effect was paralleled by a 3-fold increase in hippocampal content of CCK-8 and a smaller increase in the intermediate forms of CCK (CCK-58, CCK-39, CCK-33). Diethyldithiocarbamate also decreased the spontaneous motility and aggressiveness of the rats. These data show reversible changes of neuronal CCK processing by a drug, and hence they provide additional evidence that CCK is involved in the regulation of neuronal activities.Heavy metals occur in distinct layers of the rat hippocampus, associated with the terminal fields of certain neuronal systems, including the mossy fibers (1, 2). In the mossy fibers, there is ample evidence that most of the detectable metal is zinc (3, 4), which is located in the mossy fiber boutons (5, 6). Otherwise, the exact localization of specific metals is unknown (7).The role of zinc and other heavy metals in specific nerve terminals of the hippocampus is unknown. Recently, we have shown that both enkephalin-like molecules and heavy metals (mainly zinc) occur in the mossy fibers of rodents (8, 9). Subsequently, we have shown that zinc and other metal ions can down-regulate the binding capacity of opioid receptors (10, 11). These observations, together with the fact that endogenous opioid peptides excite hippocampal pyramidal cells via binding to opioid receptors (12), indicate that zinc, and possibly other neuronal metals, may regulate the binding capacity of opioid receptors (10, 11). The close relationship between enkephalin and zinc in the mossy fiber system may reflect that zinc is a cofactor for the recently discovered enkephalin degrading enzyme "enkephalinase" (13)(14)(15)(16).Also, cholecystokinin (CCK) nerve terminals occur closely associated with the heavy metal-containing neuropil in the rat hippocampus (8, 17). Thus, CCK immunoreactivity is located in the terminal areas of the medial perforant path and the temporo-ammonic tracts from the medial entorhinal cortex, as well as in the terminal area of the commissural-associational path of area dentata. CCK-containing cell bodies occur in all layers of the rat hippocampus, but'mostly in the stratum pyramidale, the mossy fiber zone, and the stratum radiatum (8, 17). The COOH-terminal octapeptide of 'CCK (CCK-8) appears to be a putative transmitter (18-30) wi...

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Degradation of cholecystokinin-like peptides by a crude rat brain synaptosomal fraction: A study by high pressure liquid chromatography

Cited by 81 publications

References 41 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

A serine peptidase responsible for the inactivation of endogenous cholecystokinin in brain.

Modulation of cholecystokinin concentrations in the rat hippocampus by chelation of heavy metals.

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