sincalide and ubenimex

sincalide has been researched along with ubenimex* in 6 studies

Other Studies

6 other study(ies) available for sincalide and ubenimex

ArticleYear
Characterization of a serine peptidase responsible for the inactivation of endogenous cholecystokinin in human brain.
    Neuropeptides, 1995, Volume: 28, Issue:3

    Depolarization of slices of human cerebral cortex releases cholecystokinin-8 immunoreactivity, only a fraction of which is recovered in intact immunoreactive form in the medium. This suggests that extensive hydrolysis takes place during short incubations. In the presence of diisopropylfluorophosphate, a serine reagent, the recovery is nearly doubled, however, consistent with the involvement of a serine peptidase activity. The latter was characterized by assessing the protective effects of a series of serine protease inhibitors belonging to the families of peptide chloromethylketones or boronic acids. The relative potency of these inhibitors was similar to corresponding values previously found with rat brain slices indicating that a similar serine peptidase activity is responsible for endogenous cholecystokinin inactivation in the two species.

    Topics: Amino Acid Sequence; Aminopeptidases; Animals; Cerebral Cortex; Humans; Isoflurophate; Leucine; Molecular Sequence Data; Neprilysin; Nerve Tissue Proteins; Rats; Serine Endopeptidases; Serpins; Sincalide; Thiorphan

1995
Purification and characterization of tripeptidylpeptidase-II from post-mortem human brain.
    Neurochemical research, 1993, Volume: 18, Issue:7

    A soluble tripeptidylaminopeptidase has been isolated from human post-mortem cerebral cortex by anion exchange, hydrophobic interaction and size-exclusion chromatography. From gel filtration studies the active enzyme can exist in both high molecular weight (M(r) > 10(6) and smaller forms. The enzyme hydrolyses Ala-Ala-Phe-7-amido-4-methylcoumarin with a pH optimum of around 7.5 and Km of 148 microM. It did not hydrolyse N-succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin, aminoacyl- or dipeptidyl-7-amido-methylcoumarins and was not inhibited by bestatin. The enzyme was inhibited by phenylmethylsulphonyl-fluoride, 3,4-dichloroisocoumarin, N-hydroxymercuriphenyl-sulphonic acid and N-ethylmaleimide showing that its activity is serine and cysteine dependent. The purified enzyme released tripeptides from several naturally occurring neuropeptides with quite broad specificity. Cholecystokinin octapeptide, angiotensin III and neurokinin A were the most rapidly hydrolysed. Peptides with Pro residues around the point of cleavage were not hydrolysed.

    Topics: Amino Acid Sequence; Aminopeptidases; Angiotensin III; Cerebral Cortex; Chromatography; Chromatography, Gel; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Humans; Hydrogen-Ion Concentration; Leucine; Molecular Sequence Data; Molecular Weight; Neurokinin A; Neuropeptides; Serine Endopeptidases; Sincalide; Substrate Specificity

1993
Reduction of food intake by central administration of cholecystokinin octapeptide in the rat is dependent upon inhibition of brain peptidases.
    British journal of pharmacology, 1989, Volume: 96, Issue:1

    1. The effects of intracerebroventricular (i.c.v.) injections of cholecystokinin-octapeptide (CCK-8) and caerulein, an amphibian decapeptide structurally related to CCK-8, are inconsistent in the rat. We have therefore investigated the possibility that enzymatic degradation could be responsible for the lack of activity of CCK-8 seen in some studies on food intake. 2. Injections of CCK-8 at doses of 2.5 nmol and 25 nmol into the lateral cerebral ventricle of rats did not reduce the intake of a highly palatable diet whereas injections of the same doses of caerulein reduced food intake potently and dose-dependently. 3. Co-administration of CCK-8 with a combination of the peptidase inhibitors bestatin (70 nmol), captopril (100 nmol) and thiorphan (120 nmol) resulted in an inhibition of feeding similar to that seen after the injection of caerulein alone. The peptidase inhibitors alone did not affect food intake. 4. When caerulein was injected i.c.v. in combination with bestatin, captopril and thiorphan the effect of caerulein was potentiated, suggesting that enzymatic breakdown of caerulein does occur. 5. It is concluded that the effect of centrally administered CCK-8 on food intake is dependent on the activity of cleaving enzymes in the brain. It is emphasized that the action of brain peptidases is a major factor which has to be considered when investigating the role of peptides in the central nervous system.

    Topics: Animals; Brain; Captopril; Ceruletide; Eating; Injections, Intraventricular; Leucine; Male; Protease Inhibitors; Rats; Rats, Inbred Strains; Sincalide; Thiorphan

1989
Antinociceptive action of cholecystokinin octapeptide (CCK 8) and related peptides in rats and mice: effects of naloxone and peptidase inhibitors.
    Neuropharmacology, 1987, Volume: 26, Issue:4

    Cholecystokinin octapeptide (CCK 8) produced significant antinociception in the tail immersion test in the rat, paw pressure test in the rat and acetylcholine-induced writhing test in the mouse after subcutaneous (s.c.) administration. In the hot plate test, CCK 8 (s.c.) showed antinociceptive activity if the latency to lick was used as the end point but if the latency to jump was recorded the antinociceptive effects were not evident. Cholecystokinin tetrapeptide (CCK 4) was shown to be antinociceptive in the writhing but not in the hot plate test after subcutaneous administration and appeared to be less potent than CCK 8 when tested under the same conditions. Antinociception induced by CCK 8 in the hot plate test (lick) could also be demonstrated after direct intracerebroventricular (i.c.v.) injection and this observation was also made with the CCK-related peptide FMRF amide. Antinociception induced by CCK 8 (which did not appear to be associated with reduced locomotor activity) was evident 5 min after intraventricular injection and was maximal at 10 min, the effect lasting over a 30-45 min period. The antinociceptive effect of CCK 8 was antagonised by naloxone and was potentiated by simultaneous administration of the peptidase inhibitors bestatin, thiorphan and captopril.

    Topics: Animals; Captopril; FMRFamide; Gastrins; Leucine; Male; Mice; Naloxone; Neuropeptides; Pain; Protease Inhibitors; Rats; Rats, Inbred Strains; Reaction Time; Sincalide; Tetragastrin; Thiorphan; Tiopronin

1987
Investigation on the metabolism of CCK8 analogues by rat brain slices.
    Neuropeptides, 1986, Volume: 7, Issue:1

    Degradation of Boc-CCK27-33 [Boc-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-PheNH2) a fully potent analog of CCK8 was studied on synaptic plasma membranes from pig brain cortex. Characterization of the metabolites was performed by HPLC. This allowed to show the hydrolysis of the Asp-Phe bond by the neutral endopeptidase "enkephalinase", and the cleavages at the Met-Gly and Trp-Met bonds by PCMB sensitive enzymes. Similar results were observed using Boc(diNle28,31)-CCK27-33 as substrate. To investigate the biological relevance of these enzymes in the CCK8 metabolism, the degradation studies were performed on rat brain slices, with [3H]Boc(diNle28,31)CCK27-33 as substrate. Using these more physiological preparations i.e. striatal or cortex slices, the tritiated probe was cleaved at the Nle-Gly and Gly-Trp bonds. These degradation pathways were almost completely inhibited by PCMB, but in the striatum this inhibition process induced the appearance of a small peak corresponding to the action of enkephalinase. Taken together these results seem to indicate that thiol proteases play a crucial role in the CCK8 metabolism but that enkephalinase is virtually not involved.

    Topics: Animals; Cerebral Cortex; Chloromercuribenzoates; Corpus Striatum; Hydrolysis; In Vitro Techniques; Leucine; p-Chloromercuribenzoic Acid; Peptide Fragments; Sincalide; Swine; Synaptic Membranes; Thiorphan; Tiopronin

1986
Cholecystokinin octa- and tetrapeptide degradation by synaptic membranes. I. Evidence for competition with enkephalins for in vitro common degradation pathways.
    Peptides, 1981, Volume: 2 Suppl 2

    Degradation of CCK-4 and -8 by purified synaptic membranes was followed by measuring the fluorescence of tryptophan released from the peptides after separation of degradation products by HPLC. For enkephalins and related fragments, the release of tyrosine was monitored using the same method. Kinetics of hydrolysis of CCK-like peptides indicated a rapid processing of CCK-4 and a slower breakdown of CCK-8 (with a greater resistance of the sulfated form of CCK-8 as compared to the unsulfated peptide). Leu- and met-enkephalins were degraded at the same rate while their N-terminal tri- and dipeptides were hydrolysed more slowly. When CCK-4 or CCK-8 were incubated in the presence of leu-enkephalin, a dose-dependent inhibition of the release of tryptophan was observed. Enkaphalin fragments do not modify the kinetics of degradation of CCK-4. The degradation of leu-enkephalin was inhibited in a dose-dependent manner by the presence of CCK-related peptides in the medium. After solubilization of membrane-bound enzymes by Triton X-100 followed by chromatography on DEAE cellulose, five peaks of CCK-4 degrading activity were detected (two minor and three major peaks). With enkephalin as substrate, five peaks were also observed; the three major activities were the same as those detected for CCK-4.

    Topics: Aminopeptidases; Animals; Cholecystokinin; Chromatography, DEAE-Cellulose; Endorphins; Enkephalin, Leucine; Enkephalins; Gastrins; Kinetics; Leucine; Male; Peptide Fragments; Rats; Sincalide; Synaptic Membranes; Tetragastrin; Tryptophan

1981