Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enzymatic cleavage of some peptide hormones, neurotransmitters and neuromodulators could be implicated in the regulation of extra- and intracellular fluid volume and osmolality. Prolyl endopeptidase is known to hydrolyze several peptides, which act on hydromineral balance, such as angiotensins, bradykinin, vasopressin, oxytocin, thyrotropin-releasing hormone, neurotensin and opioids. In this work, we analyzed the effects of certain volume and/or osmotic changes in the activity of the soluble and membrane-bound prolyl endopeptidase in several brain areas, heart, lungs, kidney and adrenal and pituitary glands of the rat. Soluble prolyl endopeptidase activity was higher in the renal cortex of the chronic salt-loaded rats than in the control rats. In the water-deprived and polyethylene glycol-treated rats, heart particulate prolyl endopeptidase was lower than in the control rats. Particulate prolyl endopeptidase was also lower in the adrenal gland of the acute salt-loaded rats and in the brain cortex of the water-loaded rats than in the control rats. Data suggest that tissue-dependent peptide hydrolysis evoked by prolyl endopeptidase activity is involved in the water-electrolyte homeostasis.
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PMID:Effects of hydrosaline treatments on prolyl endopeptidase activity in rat tissues. 1149 89

Prolyl endopeptidase (PEP, EC 3.4.21.26) has been proposed to play a role in degradation of proline-containing neuropeptides involved in the processes of learning and memory, e.g., vasopressin, substance P, and thyrotropin-releasing hormone (TRH). In the course of our search for bioactive constituents in medicinal plants, we studied the PEP inhibitory constituents of the roots of Lindera strychnifolia F. VILL and isolated two known tannins, epicatechin (1) and aesculitannin B (2), and four known sesquiterpenes, linderene (3), linderene acetate (4), linderalactone (5) and isolinderalactone (6) as inhibitors. On the inhibitory activities of six compounds against PEP from Flavobacterium meningosepticum and that from rat brain supernatant, compounds 1, 2 and 4 inhibited the enzyme from Flavobacterium more strongly than that from rat brain supernatant. However, compounds 3, 5 and 6 inhibited the enzymes from both origins to the same extent and furthermore, compound 6 was the strongest natural inhibitor against PEP from rat brain supernatant. The kinetic study of these inhibitors indicated that compounds 1, 2 are noncompetitive inhibitors and compounds 3-6 are competitive inhibitors. This is the first example of non-phenolic constituents showing significant competitive inhibitory activity being isolated from natural medicines.
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PMID:Prolyl endopeptidase inhibitors from the roots of Lindera strychnifolia F. Vill. 1218 8

Two peptides that inhibit prolyl endopeptidase were isolated from a red wine made from Cabernet Sauvignon grapes. Their amino acid sequences and IC50 values were Val-Glu-Ile-Pro-Glu (17.0 microM) and Tyr-Pro-Ile-Pro-Phe (87.8 microM). The peptides also suppressed the degradation levels of the bioactive peptides vasopressin, substance P, and neurotensin fragments 8-13, which are involved in memory and neural communication.
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PMID:Prolyl endopeptidase inhibitory peptides in wine. 1272 3

Prolyl endopeptidase (PEP, EC 3.4.21.26) hydrolyzes proline-containing neuropeptides, such as vasopressin, substance P, and thyrotropin-releasing hormone (TRH), and is suggested to participate in learning and memory processes. Ginkgo biloba leaves, upon examination for anti-amnestic constituents as new types of PEP inhibitors, showed significant PEP inhibition. PEP activity-guided fractionation and column chromatography of the MeOH extracts of G. biloba leaves resulted in the isolation of 6-(8'Z-pentadecenyl)salicylic acid (1) and 6-(10'Z-heptadecenyl)salicylic acid (2). The kinetic study indicated that compounds 1 and 2 are non-competitive inhibitors of prolyl endopeptidase with Ki values of 0.87 and 0.80 microM, respectively.
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PMID:Prolyl endopeptidase inhibitors from the leaves of Ginkgo biloba. 1564 62

Compound S 17092 is a potent and selective inhibitor of prolyl endopeptidase (EC 3.4.21.26, PEP) that may be of therapeutic value for the treatment of memory impairment associated with neurodegenerative diseases. In the present study, we investigated the effects of S 17092 on the catabolism of the promnesic neuropeptides thyrotrophin-releasing hormone (TRH) and arginine-vasopressin (AVP) in the rat brain. In vitro, bacterial PEP hydrolysed both TRH and AVP, and the breakdown of the two peptides was almost completely prevented by 10(-5) M S 17092. In vivo, a single oral administration of S 17092 provoked a significant increase in TRH-like immunoreactivity (TRH-LI) in the cerebral cortex (+63% for a 10 mg/kg dose and +72% for a 30 mg/kg dose), as well as AVP-LI in the hippocampus (+54% for a 30 mg/kg dose), but did not affect TRH-LI in the amygdala nor AVP-LI in the cerebral cortex. Chronic administration of S 17092 (10 or 30 mg/kg daily) lead to a significant increase in THR-LI in the cerebral cortex (+55% and +56%, respectively), but did not modify AVP-LI in the hippocampus, nor in the cerebral cortex. These results show that the selective PEP inhibitor S 17092 increases TRH and AVP content in discrete regions of the rat brain. The present data suggest that the promnesic and antiamnesic effects of S 17092 can be accounted for, at least in part, by blockage of AVP and TRH degradation by PEP.
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PMID:Effect of prolyl endopeptidase inhibition on arginine-vasopressin and thyrotrophin-releasing hormone catabolism in the rat brain. 1586 66

Prolyl oligopeptidase (POP) is a serine protease that cleaves small peptides at the carboxyl side of an internal proline residue. Substance P, arginine-vasopressin, thyroliberin and gonadoliberin are proposed physiological substrates of this protease. POP has been implicated in a variety of brain processes, including learning, memory, and mood regulation, as well as in pathologies such as neurodegeneration, hypertension, and psychiatric disorders. Although POP has been considered to be a soluble cytoplasmic peptidase, significant levels of activity have been detected in membranes and in extracellular fluids such as serum, cerebrospinal fluid, seminal fluid, and urine, suggesting the existence of noncytoplasmic forms. Furthermore, a closely associated membrane prolyl endopeptidase (PE) activity has been previously detected in synaptosomes and shown to be different from the cytoplasmic POP activity. Here we isolated, purified and characterized this membrane-bound PE, herein referred to as mPOP. Although, when attached to membranes, mPOP presents certain features that distinguish it from the classical POP, our results indicate that this protein has the same amino acid sequence as POP except for the possible addition of a hydrophobic membrane anchor. The kinetic properties of detergent-soluble mPOP are fully comparable to those of POP; however, when attached to the membranes in its natural conformation, mPOP is significantly less active and, moreover, it migrates anomalously in SDS/PAGE. Our results are the first to show that membrane-bound and cytoplasmic POP are encoded by variants of the same gene.
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PMID:Characterization of membrane-bound prolyl endopeptidase from brain. 1865 87

In vitro, prolyl oligopeptidase (POP) cleaves proline-containing bioactive peptides such as substance P, gonadotropin-releasing hormone, thyrotropin-releasing hormone, arginine-vasopressin, and neurotensin. Based on specific in vivo inhibition, POP has been suggested to be involved in cognitive and psychiatric processes but the identity of its physiological substrates has remained inconclusive. We have combined (a) sample snap-freezing and boiling buffer extraction, to limit protein degradation and reduce sample complexity; (b) pH two-dimensional liquid reverse-phase chromatography to enhance resolution; and (c) iTRAQ isobaric labeling to identify the rat brain peptides whose levels were differentially changed due to in vivo POP inhibition. In the hypothalamus, all the substrates found were part of precursors of secreted peptides such as copeptin, PACAP-related peptide, somatostatin, and proSAAS derived peptides, while in the cerebellum the peptides were derived from carcinoma-amplified sequence 1 homolog and calmodulin. In the striatum, somatostatin precursor derived peptide, fragments from E3-SUMO protein ligase RanBP2, and the subunit 5A of cytochrome c oxidase were increased. When analyzing the peptides that were significantly reduced by POP inhibition we found fragments from large protein complexes but, exclusively in the cerebellum, bioactive peptides such as cerebellin and fibrinopeptides A and B were detected.
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PMID:Combination of snap freezing, differential pH two-dimensional reverse-phase high-performance liquid chromatography, and iTRAQ technology for the peptidomic analysis of the effect of prolyl oligopeptidase inhibition in the rat brain. 1953 95


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