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)

We conducted behavioral and neurochemical studies of a novel prolyl endopeptidase inhibitor, (S)2-[[(S)-2-(hydroxyacetyl)-1pyrrolidinyl]carbonyl]-N-(phenylmeth yl)-1-pyrrolidine-carboxamide (JTP-4819), in rats with lesions of the nucleus basalis magnocellularis (NBM-lesioned rats) induced by ibotenate. Administration of JTP-4819 (1 and 3 mg/kg, p.o.), on and after the 8th day, significantly shortened the escape latency in the Morris water maze as compared to the vehicle-treated group. JTP-4819 also significantly increased the path length in the quadrant with the platform removed in the spatial probe trial. Neurochemical studies of brains removed after the Morris water maze task showed that choline acetyltransferase activity in the cerebral cortex, but not the hippocampus, was significantly reduced by NBM lesioning, while there were no changes of muscarinic M1 receptor binding activity detected using [3H]pirenzepine. JTP-4819 had almost no effect on these cholinergic parameters in NBM-lesioned rats. Substance P-like immunoreactivity (LI), thyrotropin-releasing hormone (TRH)-LI, and arginine-vasopressin-LI were not significantly changed in the cerebral cortex and hippocampus of NBM-lesioned rats as compared to sham-operated rats. However, these neuropeptide levels were significantly increased in both brain regions by repeated administration of JTP-4819 (1, 3 and/or 10 mg/kg, p.o.). These results suggest that JTP-4819 ameliorated memory impairment due to NBM lesioning by potentiating SP, TRH and AVPergic neurons secondary to PEP inhibition.
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PMID:Effect of a novel prolyl endopeptidase inhibitor, JTP-4819, on spatial memory and on cholinergic and peptidergic neurons in rats with ibotenate-induced lesions of the nucleus basalis magnocellularis. 1051 68

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

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


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