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)

Peptide hormones are synthesized from larger precursors by cleavages at paired basic residues. We have isolated a pro-hormone converting enzyme from bovine neural and intermediate lobe secretory vesicles that cleaves pro-vasopressin and pro-opiomelanocortin at Lys-Arg residues to yield vasopressin, and adrenocorticotropin/endorphin-related peptides, respectively. The enzyme from both lobes is an aspartyl protease of approximately 70,000 Da, is a glycoprotein and has an optimum pH range of 4.0-5.0. Present within the same secretory vesicles is an aminopeptidase B-like enzyme which is a metalloprotease that is inhibited by Co2+ and Zn2+. This enzyme may play a role in trimming off the N-terminal extended basic residues from peptides liberated by the pro-hormone converting enzyme.
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PMID:Pro-opiomelanocortin and pro-vasopressin converting enzyme in pituitary secretory vesicles. 284 Sep 73

Recent amino acid sequence data suggest that trypsin-like and carboxypeptidase B-like activities are required for the processing of pituitary prohormones--e.g., pro-opiocortin (pro-adrenocorticotropin/lipotropin) and provasopressin in secretory granules. In this study the existence of a carboxypeptidase B activity in purified secretory granules from anterior, intermediate, and neural lobes of rat pituitary has been examined. A carboxypeptidase B activity that cleaved the COOH-terminal -Lys-Lys-Arg residues from the adrenocorticotropin fragment ACTH-(1-17) (a potential hormone product liberated from pro-opiocortin by a trypsin-like enzyme) was detected in anterior and intermediate lobe granules. A similar carboxypeptidase B activity was also present in purified secretory granules from rat pituitary neural lobes that cleaved the -Lys-Arg residues from [Arg8]vasopressin-Gly-Lys-Arg, a potential product cleaved from provasopressin. Secretory granule carboxypeptidase(s) from the three lobes of the pituitary was shown to cleave 125I-[Met]enkephalin-Arg6 to form 125I-[Met]enkephalin as well. 125I-[Met]Enkephalin was used as a model substrate for the quantitative assay of pituitary carboxypeptidase activity. The carboxypeptidase B in secretory granules from all three lobes was shown to be active at pH 5.5, but not at pH 7.4. Inhibition by the zinc metallocarboxypeptidase inhibitors guanidinopropylsuccinic acid, aminomercaptosuccinic acid, benzylsuccinic acid, 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid, and the potato carboxypeptidase B inhibitor, and inhibition by the metal chelators EDTA and 1,10-phenanthroline demonstrate metal ion dependence of the pituitary granule carboxypeptidase activities. However, Co2+ stimulated the secretory granule carboxypeptidase B activities. Thiol protease inhibitors such as Cu2+ and p-chloromercuriphenylsulfonic acid also inhibited the activity. Thus, the secretory granule carboxypeptidase B-like activities in all three lobes of the pituitary appear to be similar thiol-metallopeptidases that differ from other carboxypeptidase activities previously described and may play an exclusive role in hormone biosynthesis in the pituitary.
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PMID:Carboxypeptidase B-like converting enzyme activity in secretory granules of rat pituitary. 632 44

Rat hepatic zinc thionein levels can be modulated by a variety of external and internal stimuli. Metals, such as zinc or copper, induce levels 20 to 50 fold over controls. Catecholamines can increase levels 10 to 20 fold, while glucocorticoids, such as dexamethasone, can increase levels modestly by 2-6 fold. We have investigated the ability of additional hormones, which have receptors on hepatocytes, to modulate the levels of hepatic zinc thionein. Glucagon, angiotensin II, and Arg-vasopressin were administered intravenously and intraperitoneally, one time and three times, over an 11 hour period. Zinc thionein levels in rat liver were increased 1.7 to 5.6 fold by glucagon and 1.7 to 3.6 fold by angiotensin II, but not at all by Arg-vasopressin, as compared to appropriate controls. Glucagon and angiotensin II, when administered in vivo, can modulate zinc thionein levels in rat liver to an extent similar to glucocorticoids. Hepatic zinc thionein levels must now be recognized to be affected in vivo by metals, glucocorticoids, catecholamines, and polypeptide hormones.
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PMID:Effects of glucagon, Arg-vasopressin, and angiotensin II on rat hepatic zinc thionein levels. 651 26

The proteolytic cleavage of a G protein-coupled peptide hormone receptor, the renal V2 vasopressin receptor, by a plasma membrane proteinase was investigated. In the absence of protease inhibitors during incubation of bovine kidney membranes with a photoreactive vasopressin agonist, V2 receptor truncation leads to a labeled receptor fragment with M(r) 30,000. The V2 receptor-degrading enzyme could be completely inhibited by zinc ions yielding the native V2 receptor glycoprotein with M(r) 58,000. Studies with inhibitors of metalloendopeptidases involved in peptide hormone metabolism and with peptide substrates spanning the V2 receptor cleavage site classify the receptor protease as metalloendoproteinase with specificity for longer substrates. Comparison of the NH2-terminal protein sequence of the truncated M(r) 30,000 V2 receptor with the sequence deduced from the cDNA of the cloned bovine V2 receptor shows that cleavage occurs between Gln92 and Val93 of the second transmembrane helix close to an extracellular agonist binding site. V2 receptor proteolysis was dependent on the presence of a hormonal ligand. It occurred rapidly after hormone binding and led to a loss of ligand binding properties of the truncated V2 receptor. The data suggest that the endogenous V2 receptor-degrading metalloendoproteinase regulates V2 receptor function. The novel pathway may contribute to the termination of signal transmission.
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PMID:Ligand-induced cleavage of the V2 vasopressin receptor by a plasma membrane metalloproteinase. 789 81

Previously it has been shown that vasopressin (VP) and oxytocin are converted by aminopeptidase activity in brain membranes into fragments with potent CNS activities. This report concerns the properties of this enzyme activity, addressed as VP-converting aminopeptidase (VP-AP) activity, in membranes of the rat brain. The VP-AP activity had a pH optimum at pH 7.0 and had a Km of 17 microM for its action on VP. Amastatin was the most potent aminopeptidase inhibitor. Enzyme activity was inhibited by relatively low concentrations of metal chelators. Treatment of brain membranes by EDTA resulted in loss of enzyme activity that was completely reversed by 10 microM Zn2+, indicating that VP-AP activity is a metallopeptidase. Several VP analogues and fragments, in particular VP(1-8), inhibited the action of enzyme activity on VP. Among peptides unrelated to VP, angiotension I, somatostatin, and porcine ACTH(1-39) markedly inhibited enzyme activity. Solubilization of VP-AP activity from brain membranes and gel filtration on Sephadex G200 showed two peaks of activity, one eluting with an apparent mass of about 140 kDa, the other in the void volume. Gel filtration fractions were able to convert [3H][Phe3]VP in a step-wise fashion. The VP-AP-like activity was found in many tissues outside the brain. Highest activity was present in lung, kidney, parts of the gastrointestinal tract, ovary, and uterus. The results indicate that VP-AP activity is a widely distributed enzyme with probably multiple functions, one of which involves the metabolism of vasopressin in the brain.
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PMID:Properties of aminopeptidase activity involved in the conversion of vasopressin by rat brain membranes. 799 91

The tetanus toxin light chain blocks calcium induced vasopressin release from neurohypophysial nerve terminals. Here we show that histidine residue 233 within the putative zinc binding motif of the tetanus toxin light chain is essential for the inhibition of exocytosis, in the rat. The zinc chelating agent dipicolinic acid as well as captopril, an inhibitor of zinc-dependent peptidases, counteract the effect of the neurotoxin. Synthetic peptides, the sequences of which correspond to motifs present in the cytoplasmic domain of the synaptic vesicle membrane protein synaptobrevin 1 and 2, prevent the effect of the tetanus toxin light chain. Our results indicate that zinc bound to the zinc binding motif constitutes the active site of the tetanus toxin light chain. Moreover they suggest that cleavage of synaptobrevin by the neurotoxin causes the inhibition of exocytotic release of vasopressin from secretory granules.
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PMID:Exploring the functional domain and the target of the tetanus toxin light chain in neurohypophysial terminals. 815 48

Adult rat primary hepatocytes maintained in DMEM/F12 (Ham) media were used as a model system for studying the role of fetal calf serum (FCS) and agonists of the phosphoinositide cascade in the metabolism of metallothionein (MT) and alkaline phosphatase (ALP). Experiments were performed both after a 24 h preincubation with FCS and with bovine serum albumin (BSA). Hepatocytes were treated with dexamethasone (DEX), zinc (Zn) and with the agonists of the phosphoinositide cascade A23187, 1,2-dioctanoyl-sn-glycerol (DiC8), 12-O-tetradecanoylphorbol-13-acetate (TPA), angiotensin II (AT), platelet activating factor (PAF), Arg8-vasopressin (VP) and were analyzed for MT and ALP activity in cell homogenates. Cell viability was evaluated by lactate dehydrogenase (LDH) liberation into culture medium, induction of tyrosine aminotransferase (TAT) through DEX and by trypan blue exclusion. Overall, cell viability was improved by the FCS pretreatment and by DEX. Exposure of hepatocytes to the established direct inducers Zn and DEX of MT resulted in a manifold increase in MT, independent of whether the cultures were FCS pretreated or not. The FCS preincubation produced a moderate elevation of ALP activity by stimulating cell viability. However, ALP was unaltered in response to Zn and DEX. None of the experiments conducted with agonists of the phosphoinositide cascade led to an elevation of MT and ALP. Only the incubation of hepatocytes with A23187 resulted in a concentration dependent significant decrease of MT and ALP. This observation was due to a cytotoxic effect of A 23187, displayed by LDH leakage and an increase in the number of cells stained with trypan blue. In conclusion, in primary hepatocyte cultures agonists of the phosphoinositide did not have an effect on the metabolism of MT and ALP. Previous in vivo results indicating alterations of Zn metabolism in liver, therefore seem to be caused by indirect systemic responses.
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PMID:Studies on the metabolism of metallothionein and alkaline phosphatase of adult rat primary hepatocyte cultures: role of fetal calf serum and agonists of the phosphoinositide cascade. 823 77

Experiments were conducted to characterize the thapsigargin-stimulated plasma membrane Ca2+ inflow pathway in hepatocytes. Ca2+ inflow was estimated by measurement of the initial rate of activation of glycogen phosphorylase a following the addition of Ca2+ to cells previously incubated in the absence of added Ca2+. Pretreatment of hepatocytes with thapsigargin caused a substantial stimulation of the rate of Ca2+ activation of glycogen phosphorylase a. This was interpreted to reflect a stimulation of plasma membrane Ca2+ inflow. The effect of thapsigargin on plasma membrane Ca2+ inflow was approximately 65% of the magnitude of the effect caused by vasopressin. When thapsigargin and vasopressin were combined as a stimulus, the degree of stimulation was similar to that caused by vasopressin alone. The thapsigargin-induced stimulation of the rate of Ca2+ activation of glycogen phosphorylase a was inhibited in a concentration-dependent manner by both Zn2+ and 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SK&F 96365). The concentration of each agent required for half-maximal inhibition was approximately 20 microM. It is concluded from: (i) the apparent lack of additivity in the responses of thapsigargin and vasopressin, and (ii) the sensitivity to inhibitors, that the Ca2+ inflow pathway in hepatocytes stimulated by thapsigargin is likely to be similar to that which is activated by vasopressin.
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PMID:Evidence that the Ca2+ inflow pathway in hepatocytes stimulated by thapsigargin is similar to that activated by vasopressin. 851 98

Several metal ions are known to cause depolymerization of the actin cytoskeleton under some circumstances. We found that in renal mesangial and vascular smooth muscle cells, micromolar concentrations of Cd2+ result in loss of phalloidinstainable filamentous (F-) actin. The decrease in F-actin was not accompanied by a corresponding increase in G-actin. The decrease in total actin could be accounted for in part by an inhibition by Cd2+ of total protein (and actin) synthesis after 6 to 8 h without an effect on actin degradation, and the equilibrium between F- and G-actin was shifted to maintain near-constant levels of G-actin. However, Cd2+ caused significant decreases in F-actin at earlier times, indicating effects on the polymerization equilibrium independent of those on actin synthesis. Only picomolar concentrations of free intracellular Cd2+ occur in these experiments. However, it is this Cd2+ pool which is responsible for F-actin depolymerization because equal cellular concentrations of cadmium delivered as Cd-metallothionein have no effect. The effect is also very specific for Cd2+ and under the same conditions neither Mg2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, nor Hg2+ result in any loss of F-actin. Addition of Cd2+ to mesangial and vascular smooth muscle cells had no immediate effect on free intracellular calcium concentrations ([Ca2+]i) even though Ca(2+)-signalling pathways were intact as shown with vasopressin and endothelin. Exposure to 10 microM CdCl2 for 8 h nevertheless caused an increase in [Ca2+]i to > 250 nM and increases in [Ca2+]i achieved with ionophores alone were sufficient to decrease F-actin concentrations. However, a rise in [Ca2+]i is not necessary for actin depolymerization. Depletion of cellular Ca2+ by treatment with thapsigargin did not protect F-actin against Cd2+; the effect of Cd2+ was enhanced in cells unable to increase their [Ca2+]i. We conclude that depolymerization of F-actin by Cd2+ in smooth muscle and mesangial cells is metal-specific, Ca(2+)-independent, and accompanied by a depletion of total actin protein.
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PMID:Calcium-independent effects of cadmium on actin assembly in mesangial and vascular smooth muscle cells. 867 40

Arg8-vasopressin (AVP) is a potent inducer of myogenic differentiation stimulating the expression of myogenic regulatory factors. To understand the mechanism of its effect on myogenesis, we investigated the early signals induced by AVP in myogenic target cells. In the rat skeletal muscle cell line L6, AVP selectively stimulates phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho) breakdown, through the activation of phospholipases C and D (PLC, PLD), as shown by the generation of Ins(1,4,5)P3 and phosphatidylethanol (PtdEtOH), respectively. AVP induces the biphasic increase of sn-1,2-diacylglycerol (DAG) consisting in a rapid peak followed by a sustained phase, and the monophasic generation of phosphatidic acid (PA). Propranolol (a PA phosphatase inhibitor) and Zn2+ (a PLD inhibitor), abolish the sustained phase of DAG generation. Our data indicate that PtdIns-PLC activity is mainly responsible for the rapid phase of AVP-dependent DAG generation, whereas the sustained phase is dependent upon PtdCho-PLD activity and PA dephosphorylation, ruling out any significant role of DAG kinase. Modifications of PA level correlate with parallel changes of PLC activity, indicating a possible cross-talk between the two signal transduction pathways in the intact cell. PLD activation is elicited at AVP concentrations two orders of magnitude lower than those required for PLC activation. The differentiation of L6 myoblasts into multinucleated fibers is stimulated significantly by AVP at concentrations at which PLD, but not PLC, is activated. These data provide the first evidence for an important role of PLD in the mechanism of AVP-induced muscle differentiation.
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PMID:Role of phospholipase C and D signalling pathways in vasopressin-dependent myogenic differentiation. 911 90


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