UNIPROT:P01185 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P01185 (vasopressin)
23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inactivation of the neurohypophyseal hormones arginine vasopressin and oxytocin, both 14C-labelled in the C-terminal glycine residue, by enzymes present in kidney homogenates of various species has been investigated, and some of the enzymes responsible have been partially purified and characterized. The Leu-Gly peptide bond of oxytocin is generally most effectively cleaved by kidney homogenates, although with certain species enzymic activity hydrolyzing the Pro-Leu bond is significant. Degradation of arginine vasopressin is slower than oxytocin in all species studied, and appears to occur by a different overall mechanism since cleavage of the Pro-Arg bond is more significant than hydrolysis of the Arg-Gly bond. The enzyme releasing glycinamide from oxytocin and the "Post-Proline Cleaving Enzyme", which releases C-terminal dipeptide from oxytocin and arginine vasopressin, were partially purified from lamb kidney by ammonium sulfate fractionation and column chromatography. The two enzymes are shown to be separate entities with different pH profiles. The prolyl peptidase activity released the C-terminal dipeptides from oxytocin and arginine vasopressin at similar rates and was inhibited by p-chloromercuriphenylsulfonic acid, 1,10-phenanthroline, L-1-tosylamido-2-phenylethylchloromethyl ketone, Co2+, Ca2+, and Zn2+, but significantly enhanced by dithiothreitol. The prolyl peptidase preparation cleaves proline-containing peptide substrates at the Pro-X bond. The rate of cleavage is dependent on the nature of residue X and with the conditions used there is no cleavage when X equals Pro; however, cleavage occurs when X is a D isomer: [Mpr1, D-Arg8] vasopressin is inactivated at a rate similar to [Mpr1, Arg8]- and [Mpr1, Lys8] vasopressin, suggesting that the known prolonged biological action of [Mpr1, D-Arg8] vasopressin is not due to resistance to the prolyl peptidase. In all characteristics tested the lamb kidney prolyl peptidase was identical to the post-proline cleaving enzyme isolated earlier from human uterus. In vivo experiments in the cat suggested that both the glycinamide-releasing enzyme and post-proline cleaving enzyme are present and effective in inactivating neurohypophyseal hormones in the intact animal.
...
PMID:Partial purification and characterization of post-proline cleaving enzyme: enzymatic inactivation of neurohypophyseal hormones by kidney preparations of various species. 0

1. Proline endopeptidase (E.C.3.4.21.26) is an enzyme which cleaves several peptides at the carboxyl side of proline residues. Because brain contains relatively large amounts of this enzyme and because of its specificity it has been suggested that it plays a role in the metabolism of neuropeptides, acting both on their processing and their degradation. 2. Since the final steps of neuropeptide processing occur in the synaptic vesicles and the degradation of most of these peptides is believed to occur in the synaptic cleft, we studied the distribution of proline endopeptidase activity in sub-fractions of rat hypothalamus. 3. Proline endopeptidase activity is present in synaptosomal fractions and is released by hypo-osmotic shock. Its specific activity is higher in the synaptoplasma than in synaptic membranes or vesicles (7.98 vs 0.18 and 0.24 nmol min-1 mg protein-1 carbobenzoxy-glycyl-prolyl-sulfamethoxazole hydrolysis). 4. Inhibitory avoidance training, a situation which releases hypothalamic vasopressin and beta-endorphin, both in vitro substrates, did not affect the specific or total activity of proline endopeptidase in synaptosomal plasma membranes.
...
PMID:Distribution of proline endopeptidase activity in sub-synaptosomal fractions of rat hypothalamus. 330 57

Proline endopeptidase (E.C.3.4.21.26) is an enzyme which cleaves several neuropeptides at the carboxyl-side of proline residues. Some peptide substrates of this enzyme may be found in the rat hypothalamus (thyrotropin releasing hormone, neurotensin, substance P, oxytocin, vasopressin, beta-endorphin). Recent research has shown that the hypothalamic levels of some of these substances (e.g., vasopressin, beta-endorphin) change by a variety of training procedures. We studied the effect of various forms of training on the activity of proline endopeptidase of rat hypothalamus. The present results show that the activity of this enzyme is not altered by electroconvulsive shock or inhibitory avoidance training when measured, 0, 1, or 3 hr after these procedures. Other behavioral procedures (habituation to an open field, two-way active avoidance conditioning, or 1 min of inescapable footshock) also had no effect on hypothalamic proline endopeptidase activity measured immediately after training or test sessions. We conclude that proline endopeptidase probably does not play a regulatory role in the effect of synaptically released hypothalamic neuropeptides on behavior.
...
PMID:Hypothalamic proline endopeptidase activity is not changed by various behavioral procedures. 353 16

Vasoactive peptides contain a high proportion of proline residues which make them resistant to hydrolysis by many peptidases. However, post proline cleaving enzyme (PPCE; EC 3.4.21.26), a proline specific endopeptidase which specifically hydrolyzes internal peptide bonds on the carboxyl side of proline residues, has been shown to inactivate numerous vasoactive peptides including angiotensins, kinins, substance P, vasopressin and oxytocin. In order to determine whether PPCE could be involved in vascular metabolism of vasoactive peptides, we carried out localization and characterization studies of PPCE-like activity in hog aorta and mesenteric artery. PPCE was assayed fluorometrically at pH 7.0 using the specific PPCE substrate CBZ-Gly-Pro-4-methyl-coumarinylamide. The subcellular distribution of vascular PPCE was essentially the same as that of the cytosolic marker enzyme lactic dehydrogenase (LDH). PPCE was enriched six-fold in the cytosolic fraction (11.4 +/- 2.7 units/mg) and unlike the plasma membrane-bound proline specific exopeptidase dipeptidyl-(amino)peptidase IV (DAP IV; EC 3.4.14.5), little or no activity could be detected in the microsomal or plasma membrane fractions. Similar to PPCE characterized from other sites, vascular PPCE was stabilized and activated by dithiothreitol and EDTA, and inhibited by DFP, p-chloromercuriphenyl sulfonic acid, L-1-tosylamido-2-phenylethylchloromethyl ketone, Cu++, Ca++, and Zn++. Vascular PPCE was unaffected by inhibitors of trypsin and kallikrein (Aprotinin, ABTI), aminopeptidase M (bestatin, amastatin), neutral endopeptidase (phosphoramidon), angiotensin I converting enzyme (captopril) or carboxypeptidase N (MERGETPA). These data demonstrate that PPCE is present in vascular endothelium and/or smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Vascular, post proline cleaving enzyme: metabolism of vasoactive peptides. 354 18

A post-proline cleaving enzyme [prolyl endopeptidase, EC 3.4.21.26] was purified about 3,700-fold from an extract of bovine brain by a series of column chromatographies on DEAE-Sephadex, hydroxyapatite and PCMB-T-Sepharose, and gel filtration on Sephadex G-200 using N-carbobenzoxy-Gly-Pro-beta-naphthylamide (Z-Gly-Pro-2-NNap), thyrotropin releasing hormone (TRH) and oxytocin as substrates. The purified enzyme appeared homogeneous as judged by disc gel and SDS gel electrophoreses. The enzyme was most active at pH 7.5 and 7.2 with Z-Gly-Pro-2-NNap and TRH, respectively, and hydrolyzed peptide bonds involving Pro-X (X=amino acid, peptide, ester and amide) bonds of synthetic substrates, oxytocin, vasopressin, neurotensin, substance P, tuftsin, bradykinin, and insulin B chain. However, the enzyme was inert toward collagen, gelatin, and casein. The enzyme was completely inactivated by diisopropylphosphorofluoridate (DFP), Z-Gly-Pro-chloromethyl ketone and p-chloromercuribenzoate (PCMB), while it was not inhibited by phenylmethane sulfonylfluoride (PMSF) or metal chelators. Determination of the amino acid composition revealed that the enzyme contained 25 half-cystines. Modification of three cysteine residues of the enzyme by PCMB led to complete inactivation. The isoelectric point of the enzyme was 4.8, and the molecular weight was estimated to be 76,000 by ultracentrifugal analysis and 75,000-74,000 by both gel filtration and sodium dodecyl sulfate (SDS) gel electrophoresis, suggesting that the enzyme is present as a monomer. These results indicate that the post-proline cleaving enzyme from bovine brain is very similar to those previously purified from lamb brain and kidney in its enzymatic properties, substrate specificity and physicochemical properties, in sharp contrast with the results obtained by Tate, who reported that the bovine brain prolyl endopeptidase was inert toward oxytocin, vasopressin and bradykinin.
...
PMID:Post-proline cleaving enzyme (prolyl endopeptidase) from bovine brain. 636 Oct 10

A post-proline cleaving enzyme [post-proline endopeptidase: EC 3.4.21.26] was purified from lamb brain by a series of column chromatographies on DEAE-Sephadex, hydroxyapatite and Sephadex G-150. The purified enzyme appeared homogeneous on disc gel and sodium dodecyl sulfate (SDS) gel electrophoreses. The enzyme was most active at pH 7.0 with carbobenzoxy-Gly-Pro-beta-naphthylamide (Z-Gly-Pro-2-NNap) as a substrate and catalyzed the hydrolysis of oxytocin, vasopressin, thyrotropin releasing hormone (TRH), substance P, luteinizing hormone releasing hormone (LH-RH), and angiotensin at the carboxyl side of their proline residues, except for the Pro2-Lys3 bond in substance P. From the results of subsite mapping using synthetic peptides, five subsites, S3 to S2', for substrate interaction with the enzyme were deduced to be present, and high stereospecificity was observed at S2, S1, and S1'. The isoelectric point of the enzyme was at pH 4.9, and the molecular weights estimated by gel filtration and SDS gel electrophoresis were 74,000 and 77,000, respectively. The enzyme was markedly inhibited by diisopropylphosphoro fluoridate (DFP), carbobenzoxy-Gly-Pro-chloromethyl ketone (Z-Gly-Pro-CH2Cl), p-chloromercuribenzoate (PCMB), Hg2+, and Cu2+ ions. These enzymatic and protein chemical properties of post-proline cleaving enzyme from lamb brain closely resemble those of the lamb kidney enzyme, except for the molecular weight. In the present work, however, we decided that the molecular weight of the enzyme from lamb kidney was also 74,000, which is different from that reported previously (J. Biol. Chem. 251, 7593 (1976) but is in accord with the value of post-proline cleaving enzyme from lamb brain.
...
PMID:Post-proline cleaving enzyme from lamb brain. 702 30

Prolyl endopeptidase (PEP; EC 3.4.21.26) cleaves the Pro-Arg bond of arginine-vasopressin (AVP). This study investigated the effects of PEP inhibitors, 1-[1-(benzyloxycarbonyl)-L-prolyl]prolinal (Z-Pro-prolinal) and 1-[3-(2-indanylacetyl)-L-thioprolyl]pyrrolidine (Z-321), on the AVP content in the septum of rats. Oral administration of Z-Pro-prolinal (100 mg/kg) and Z-321 (100 mg/kg) significantly increased the septal AVP content. At 10 mg/kg, Z-321 slightly increased the content. In contrast, the D-thioprolyl form of Z-321 (100 mg/kg), which lacks an inhibitory effect on the enzyme, failed to affect the AVP content. These results indicate that PEP inhibitors increase the content of AVP through inhibition of the enzyme activity in vivo. Therefore, it is suggested that PEP may contribute to the degradation of endogenous AVP in the brain.
...
PMID:Increase in the septal vasopressin content by prolyl endopeptidase inhibitors in rats. 750 Dec 40

An endo-acting proline-specific oligopeptidase (prolyl oligopeptidase [POPase], EC 3.4.21.26) was purified to homogeneity from the Triton X-100 extracts of cells of Treponema denticola ATCC 35405 (a human oral spirochete) by a procedure that comprised five successive fast protein liquid chromatography steps. The POPase is a cell-associated 75- to 77-kDa protein with an isoelectric point of ca. 6.5. The enzyme hydrolyzed (optimum pH 6.5) the Pro-pNA bond in carbobenzoxy-Gly-Pro-p-nitroanilide (Z-Gly-Pro-pNA) and bonds at the carboxyl side of proline in several human bioactive peptides, such as bradykinin, substance P, neurotensin, angiotensins, oxytocin, vasopressin, and human endothelin fragment 22-38. The minimum hydrolyzable peptide size was tetrapeptide P3P2P1P'1, while the maximum substrate size was ca. 3 kDa. An imino acid residue in position P1 was absolutely necessary. The hydrolysis of Z-Gly-Pro-pNA was potently inhibited by the following, with the Ki(app) (in micromolar) in parentheses: insulin B-chain (0.7), human endothelin-1 (0.5), neuropeptide Y (1.7), substance P (32.0), T-kinin (4.0), neurotensin (5.0), and bradykinin (16.0). Chemical modification and inhibition studies suggest that the POPase is a serine endopeptidase whose activity depends on the catalytic triad of COOH ... Ser ... His but not on a metal. The amino acid sequence around the putative active-site serine is Gly-Gly-Ser-Asn-Pro-Gly. The enzyme is suggested to contain a reactive cysteinyl residue near the active site. Amino acid residues 4 to 24 of the first 24 N-terminal residues showed a homology of 71% with the POPase precursor from Flavobacterium meningosepticum and considerable homology with the Aeromonas hydrophila POPase. The ready hydrolysis of human bioactive peptides at bonds involving an imino acid residue suggests that enzymes like POPase may contribute to the chronicity of periodontal infections by participating in the peptidolytic processing of those peptides.
...
PMID:An endo-acting proline-specific oligopeptidase from Treponema denticola ATCC 35405: evidence of hydrolysis of human bioactive peptides. 752 1

A measuring method sensitive to prolyl endopeptidase (EC 3.4.21.26, PEP) activity using native peptides (Arg-vasopressin or substance P) as substrates was established. The investigation of three different derivatization reagents, which had been developed for an amino acid analysis, demonstrated that 4-fluoro-7-nitrobenzo-2-oxa-1,3-diazole (NBDF) was the most suitable for the detection of Arg-Gly-NH2, which was released from Arg-vasopressin by PEP. Arg-Gly-NH2 was reacted with NBDF at 65 degrees C for 5 min at pH 7.6 and the reaction mixture was analysed by HPLC on a reverse-phase column by monitoring the fluorescence intensity. The detection limit was 1 picomol per injection and the linear standard calibration curve could be constructed in the range of 1 to 100 picomol per injection with a 3.0% relative standard deviation. This sensitive detection method for peptide was applied to the measurement of PEP activity using Arg-vasopressin as a substrate and 1 x 10(-3) unit of PEP activity was detectable. This method was also applicable to the measurement of PEP activity using substance P as a substrate by detecting the derivative of its fragment peptide (Arg-Pro-Lys-Pro).
...
PMID:A sensitive detection method for peptide using 4-fluoro-7-nitrobenzo-2-oxa-1,3-diazole and its application to measure prolyl endopeptidase activity. 753 49

The effects of a novel prolyl endopeptidase (PEP) inhibitor, (S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N-(phenylmethyl) - 1-pyrrolidinecarboxamide (JTP-4819), on the PEP activity in the brain and on the contents of substance P (SP)- and arginine-vasopressin (AVP)-like immunoreactivity (LI) in the cerebral cortex and hippocampus of young and aged rats were investigated using enzyme immunoassay. JTP-4819 exhibited a concentration-dependent in vitro inhibitory action on PEP activity in the brains of both young and aged rats, with IC50 values of approximately 0.7 and 0.8 nM, respectively. A single dose of JTP-4819 (3 mg/kg, p.o.) increased the SPLI content in the cerebral cortex but not the hippocampus of aged rats (23-24 months old). In addition, repeated administration of JTP-4819 (1 mg/kg, p.o., for 21 days) increased the SPLI content in the cerebral cortex and restored the SPLI content in the hippocampus, which had decreased with aging. In contrast, single (1 mg/kg, p.o.) and repeated (1 mg/kg, p.o., for 21 days) administration of JTP-4819 only tended to increase the AVPLI content of the hippocampus and cerebral cortex in aged rats, respectively. These results indicate that JTP-4819 increases the cerebral and hippocampal SPLI content in aged rats by inhibiting the action of PEP.
...
PMID:Effect of a novel prolyl endopeptidase inhibitor, JTP-4819, on prolyl endopeptidase activity and substance P- and arginine-vasopressin-like immunoreactivity in the brains of aged rats. 754 Jun 63

1 2 3 Next >>