Cholecystokinin octa- and tetrapeptide degradation by synaptic membranes. I. Evidence for competition with enkephalins for in vitro common degradation pathways

Deschodt-Lanckman, M; Bui, Ngoc Diem

doi:10.1016/0196-9781(81)90021-8

Cited by 29 publications

(5 citation statements)

References 23 publications

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“…APN is a zinc-containing proteolytic ectoenzyme recently cloned (Olsen et al, 1988;Watt and Yip, 1989). In the brain, APN has been shown to be involved in the degradation of the opioid peptides, enkephalins (Waksman et al, 1985;Turner et al, 1987), dynorphin , and cholecystokinin octapeptide (Deschodt-Lanckman and Bui, 1981;Durieux et al, 1986). The membrane-bound APN has a broad specificity (McDonald and Barrett, 1986), although hydrophobic residues, preferentially aromatic, in the NH2-terminal position are more rapidly removed.…”

Section: Discussionmentioning

confidence: 99%

Nociceptin/Orphanin FQ Metabolism: Role of Aminopeptidase and Endopeptidase 24.15

Montiel

Cornille

Roques

et al. 1997

Journal of Neurochemistry

104

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The endogenous opioid receptor‐like1 (ORL1) ligand, nociceptin/orphanin FQ (FGGFTGARKSARKLANQ), a heptadecapeptide structurally resembling dynorphin A, has recently been identified. The wide distribution of ORL1 mRNA and nociceptin/orphanin FQ precursor in the CNS, particularly in the limbic system regions and in several areas known to be involved in pain perception, suggests that nociceptin/orphanin FQ is potentially endowed with various central functions. In general, activation and/or inactivation of regulatory peptides occur through the action of cell surface peptidases. The physiological mechanisms under which nociceptin/orphanin FQ is metabolized should lead to a better understanding of its physiological functions. Mouse brain cortical slices were incubated in medium containing the heptadecapeptide in the presence or in the absence of peptidase inhibitors. The critical sites of enzymatic cleavage are Phe1‐Gly2, Ala7‐Arg8, Ala11‐Arg12, and Arg12‐Lys13 bonds. The major role played by metallopeptidases was confirmed by the complete protection of metabolism in the presence of EDTA. Aminopeptidase N and endopeptidase 24.15 are the two main enzymes involved in nociceptin/orphanin FQ metabolism, whereas endopeptidase 24.11 (involved in enkephalin [YGGFM(L)] catabolism) does not appear critically involved in nociceptin/orphanin FQ metabolism. The physiological relevance of aminopeptidase N and endopeptidase 24.15 in the heptadecapeptide metabolism remains to be determined.

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Section: Discussionmentioning

confidence: 99%

Nociceptin/Orphanin FQ Metabolism: Role of Aminopeptidase and Endopeptidase 24.15

Montiel

Cornille

Roques

et al. 1997

Journal of Neurochemistry

104

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“…DPPIV has been implicated in the degradation of several hormones and peptides such as peptide YY, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide-1 (53). Degradation of CCK-8 and smaller CCK fragments by plasma aminopeptidases has been studied by Deschodt-Lanckman et al (11). Tyrosine residues and the amino acids methionine and glycine in the sequence of CCK are cleaved by aminopeptidases at a higher rate than tryptophan (30).…”

Section: Discussionmentioning

confidence: 99%

Effect of intraperitoneal and intravenous administration of cholecystokinin-8 and apolipoprotein AIV on intestinal lymphatic CCK-8 and apo AIV concentration

Lo¹,

Xu²,

Yang³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…CCK-8 has been shown to be processed by membrane-bound and cytosolic synaptosomal. enzymes (2,3). The physiological significance of CCK-8 degradation by soluble enzymes remains unclear while it is conceivable that synaptic membrane bound proteases are involved in the inactivation of neuropeptides after their discharge in the synaptic cleft.…”

Section: Discussionmentioning

confidence: 99%

“…Kinetics of the hydrolysis of these peptides at 37°C by purified synaptic membranes were previously published (2). The presence of increasing amounts of proglumide in the incubation medium inhibited the cleavage of CCK-8 (50 /1M) or leuenkephalin (500 ttlvl) by the purified synaptic membranes, with D59 of 1.6 and 0.7 mM respectively (Fig.…”

Section: Dose-efliect Curves Of Proglumide On the Degradation Of Cck-mentioning

confidence: 99%

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<b>PROGLUMIDE INHIBITS THE DEGRADATION OF CHOLECYSTOKININ OCTAPEPTIDE AND LEUCINEENKEPHALIN BY BRAIN </b><b>ENZYMES </b>

Lanckman¹,

Bui²

1982

Biomed. Res.

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Proglumide, a derivative of glutaramic acid which has been used for many years in the treatment of ulcers, was found to inhibit the degradation of the C-terminal octapeptide (CCK-8) of cholecystokinin (CCK) by brain enzymes. Another antagonist of CCK-gastrin receptors, dibutyryl cyclic GMP had no effect. The effect of proglumide was not specific for CCK peptides since the cleavage of the N-terminal tyrosine residue of leucine-enkephalin by brain enzymes was also inhibited. The inhibition did not involve CCK receptors as it was observed for the degradation of CCK-8 by cytosolic synaptosomal enzymes as well as for the cleavage of the peptide by purified synaptic membranes. The inhibition exerted by proglumide on the degradation of unsulfated CCK-8 by synaptic membranes displayed a non-competitive character with an apparent Ki value of 1.3 mM. Two non-competitive K, values (0.6 and 2.0 mM) were found for the inhibition of the cleavage of leu-enkephalin. Proglumide inhibited the degradation of CCK-8 by brain enzymes but was ineifective towards the cleavage of this peptide by pancreatic plasma membranes. Comparison of the structure of proglumide with aminopeptidase inhibitors shows some similarities between these molecules and suggests that this compound might act through the same mechanism on brain CCK-8 and leu-enkephalin degrading aminopeptidases.

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Cholecystokinin octa- and tetrapeptide degradation by synaptic membranes. I. Evidence for competition with enkephalins for in vitro common degradation pathways

Cited by 29 publications

References 23 publications

Nociceptin/Orphanin FQ Metabolism: Role of Aminopeptidase and Endopeptidase 24.15

Nociceptin/Orphanin FQ Metabolism: Role of Aminopeptidase and Endopeptidase 24.15

Effect of intraperitoneal and intravenous administration of cholecystokinin-8 and apolipoprotein AIV on intestinal lymphatic CCK-8 and apo AIV concentration

<b>PROGLUMIDE INHIBITS THE DEGRADATION OF CHOLECYSTOKININ OCTAPEPTIDE AND LEUCINEENKEPHALIN BY BRAIN </b><b>ENZYMES </b>

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