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)

Although glycogen synthase is present in a highly inactivated state in hepatocytes from streptozocin-induced diabetic rats, glucagon, vasopressin, and vanadate are still able to further decrease the basal activity of the enzyme. This inactivation was observed with the low-to-high glucose 6-phosphate activity ratio assay. The inactivation of glycogen synthase occurred concomitantly with the activation of glycogen phosphorylase. When hepatocytes from diabetic rats were incubated with [32P]phosphate and then with the agents and when the 32P-labeled glycogen synthase was immunoprecipitated, we observed that the 32P bound to the 88,000-Mr subunit increased in all cases. All the [32P]phosphate was located in two cyanogen bromide fragments of the enzyme, indicating that the enzyme was phosphorylated at multiple sites. The fragments were precisely those phosphorylated by glycogenolytic hormones in hepatocytes from normal rats. These results demonstrated that hepatic glycogen synthase, although highly inactive, is under potential hormonal control in diabetes and that the enzyme has not reached its maximal level of phosphorylation. Furthermore, they indicated that vanadate behaves as a glycogenolytic agent regarding its effects on glycogen-metabolizing enzymes in hepatocytes from diabetic rats.
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PMID:Control of glycogen synthase and phosphorylase in hepatocytes from diabetic rats. Effects of glucagon, vasopressin, and vanadate. 249 42

Incubation of isolated rat hepatocytes with oxytocin produces a time- and dose-dependent inactivation of glycogen synthase. Such inactivation is associated with an increase in the phosphorylation state of the 88 kDa subunit of the enzyme, as observed after electrophoretic analysis of the 32P-labelled enzyme isolated by immunoprecipitation from cells incubated with [32P]phosphate. CNBr cleavage of the immunoprecipitated glycogen synthase showed that multiple sites were phosphorylated after exposure of the cells to the hormone. The effect of oxytocin on hepatocyte glycogen synthase activity was not observed in the absence of extracellular Ca2+. Inactivation of glycogen synthase by oxytocin was partially abolished in the presence of insulin. These results indicate that the effects of oxytocin on glycogen synthase from rat hepatocytes are similar to those observed for other Ca2+-mediated glycogenolytic hormones, such as vasopressin.
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PMID:Oxytocin inactivates and phosphorylates rat hepatocyte glycogen synthase. 250 22

The regulation of transepithelial water permeability in toad urinary bladder is believed to involve a cycling of endocytic vesicles containing water transporters between an intracellular compartment and the cell luminal membrane. Endocytic vesicles arising from luminal membrane were labeled selectively in the intact toad bladder with the impermeant fluid-phase markers 6-carboxyfluorescein (6CF) or fluorescein-dextran. A microsomal preparation containing labeled endocytic vesicles was prepared by cell scraping, homogenization, and differential centrifugation. Osmotic water permeability was measured by a stopped-flow fluorescence technique in which microsomes containing 50 mM mannitol, 5 mM K phosphate, pH 8.5 were subject to a 60-mM inwardly directed gradient of sucrose; the time course of endosome volume, representing osmotic water transport, was inferred from the time course of fluorescence self-quenching. Endocytic vesicles were prepared from toad bladders with hypoosmotic lumen solution treated with (group A) or without (group B) serosal vasopressin at 23 degrees C, and bladders in which endocytosis was inhibited by treatment with vasopressin at 0-2 degrees C (group C), or with vasopressin plus sodium azide at 23 degrees C (group D). Stopped-flow results in all four groups showed a slow rate of 6CF fluorescence decrease (time constants 1.0-1.7 s for exponential fit) indicating a component of nonendocytic 6CF entrapment into sealed vesicles. However, in vesicles from group A only, there was a very rapid 6CF fluorescence decrease (time constant 9.6 +/- 0.2 ms, SEM, 18 separate preparations) with an osmotic water permeability coefficient (Pf) of greater than 0.1 cm/s (18 degrees C) and activation energy of 3.9 +/- 0.8 kcal/mol (16 kJ/mol). Pf was inhibited reversibly by greater than 60% by 1 mM HgCl2. The rapid fluorescence decrease was absent in vesicles in groups B, C, and D. These results demonstrate the presence of functional water transporters in vasopressin-induced endocytic vesicles from toad bladder, supporting the hypothesis that water channels are cycled to and from the luminal membrane and providing a functional marker for the vasopressin-sensitive water channel. The calculated Pf in the vasopressin-induced endocytic vesicles is the highest Pf reported for any biological or artificial membrane.
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PMID:Very high water permeability in vasopressin-induced endocytic vesicles from toad urinary bladder. 251 41

Arginine vasopressin (AVP)-induced formation of inositol phosphates and increased calcium efflux in smooth muscle cells (A-10) were inhibited by short term treatment with phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C (Ca2+/phospholipid-dependent protein kinase) (Aiyar, N., Nambi, P., Whitman, M., Stassen, F. L., and Crooke, S. T. (1987) Mol. Pharmacol. 31, 180-184). Here we report that prolonged treatment of A-10 cells (48 h) with PDBu markedly enhanced AVP-induced calcium mobilization but inhibited ATP- and thrombin-induced calcium mobilization. PDBu (400 nM) doubled [Ca2+]i induced with 3 nM AVP, while the basal calcium concentrations before and after AVP were not different from those of untreated cells. The EC50 for a 24-h exposure was 2.3 nM PDBu. Phorbol 12-myristate 13-acetate was also effective, while 4-alpha-phorbol 12,13-didecanoate (48 h at 400 nM) was without effect. 4-alpha-phorbol 12,13-didecanoate also did not affect inositol phosphate formation. PDBu markedly enhanced inositol phosphate formation induced by AVP but not by NaF. PDBu did not affect basal inositol phosphate and polyphosphoinositide levels, and cytosolic and membrane-associated phospholipase C activity. PDBu treatment (48 h, 400 nM) decreased membrane-associated and cytosolic protein kinase C activity by 80 and 90%, respectively. However, the dose response and time course of changes in protein kinase C activity did not correlate with the same curves for PDBu enhancement of AVP-induced calcium mobilization. We conclude that prolonged PDBu treatment selectively enhanced AVP-induced calcium mobilization and polyphosphoinositide hydrolysis. These effects were not caused by an increase in vasopressin receptor number and apparent affinity, an increase in phospholipase C activity, G-protein-phospholipase C coupling, formation of polyphosphoinositide, or inhibition of inositol phosphate metabolizing enzymes. Enhancement of the AVP responses did not correlate with desensitization or activation of protein kinase C. We suggest that prolonged PDBu treatment might sensitize a putative V1 receptor-G-protein-phospholipase C complex.
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PMID:Prolonged incubation with phorbol esters enhanced vasopressin-induced calcium mobilization and polyphosphatidylinositol hydrolysis of vascular smooth muscle cells. 252 48

As previously described, WRK1 plasma membrane possesses a vasopressin-sensitive phospholipase C [G. Guillon et al., 1986, FEBS Lett. 196, 155-159]. In the present study, we examined the sensitivity of this enzyme to guanylnucleotides. GTP gamma S induces a time- and dose-dependent stimulation of Ins(1,4,5)P3 and Ins(1,4)P2 accumulation. No accumulation of InsP1, Ins(1,3,4)P3 or Ins(1,3,4,5)P4 occurred under similar conditions. Gpp(NH)p produced the same effect but was less potent. GTP and a nonhydrolyzable analogue of ATP, App(NH)p, were without effect. Calcium also stimulated the phospholipase C activity in a time- and dose-dependent manner. In the absence of calcium, the activity of GTP gamma S was considerably reduced. Physiological calcium concentrations (between 10(-8) and 10(-7) M), allowed maximal GTP gamma S stimulation of phospholipase C activity. In this system, the presence of vasopressin alone did not generate inositol phosphate accumulation. However, this hormone: (i) reduced the lag-time observed during GTP gamma S stimulation, (ii) increased the sensitivity of phospholipase C to GTP and to GTP gamma S, and (iii) did not modify the stimulation of phospholipase C induced by maximal doses of GTP gamma S. Unlike sodium fluoride, GTP gamma S elicited an irreversible activation of phospholipase C. Calcium, GTP gamma S and sodium fluoride stimulated the phospholipase C activity via mechanisms sharing a common step, since their maximal effects were not additive. Cholera toxin treatment, known to produce complete ADP-ribosylation of 'alpha s' subunits, partially reduced the basal and the maximal GTP gamma S-mediated stimulation of phospholipase C activity as well as that caused by vasopressin. This inhibition was not mimicked by treatment with either forskolin or pertussis toxin.
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PMID:Properties of membranous phospholipase C from WRK1 cell: sensitivity to guanylnucleotides and bacterial toxins. 253 43

Vasopressin stimulated phospholipase C activity in primary cultures of rat hepatocytes maintained for 18-24 h under serum free conditions. Soluble and membrane-associated phospholipase C activity was determined using exogenous [3H]phosphatidylinositol 4,5-bisphosphate ([3H]PIP2) in the presence of cholate, deoxycholate and NaCl. Exposure of hepatocytes for 5 s to vasopressin (100 nM) stimulated both membrane-associated and soluble phospholipase C activity by 30% and 40%, respectively. However, by 15 s this stimulation had disappeared. Addition of vasopressin to hepatocytes, previously labelled with [3H]inositol, stimulated inositol phosphate production within 5 s, but little further increase was seen over a 5-min incubation. These results indicate that vasopressin rapidly stimulates both soluble and membrane-associated phospholipase C activity.
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PMID:Vasopressin transiently stimulates phospholipase C activity in cultured rat hepatocytes. 253 85

The hormonal regulation of phosphoinositide levels in isolated hepatocytes was studied using chemical means. Extracted inositol phospholipids were adsorbed to neomycin-coated glass beads and then eluted and quantitated by charring after separation by thin layer chromatography on silica gel. The amounts (in nanograms/mg wet weight) of phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP), and phosphatidylinositol (PI) were 20 +/- 1, 16 +/- 1, and 1790 +/- 140, respectively). Incubation of the cells with 100 nM vasopressin decreased the value for PIP2 to 10 +/- 0.2 at 15 s, 12 +/- 1.5 at 1 min, and 14 +/- 2.1 at 5 and 30 min. In contrast, the hormone increased 1,2-diacylglycerol plus phosphatidate by over 200 ng/mg wet weight at 5 min under similar conditions (Bocckino, S. B., Blackmore, P. F., Wilson, P. B., and Exton, J. H. (1987) J. Biol. Chem. 262, 15309-15315). PIP2 was also significantly decreased at 15 s by angiotensin II (100 nM), ATP (100 microM), and epinephrine (1 microM). In contrast, PIP was not significantly changed, and PI was significantly decreased (by approximately 15%) at later times (15 and 30 min). The changes in phosphoinositide mass were well correlated with changes in labeled phosphoinositides in hepatocytes previously incubated with [3H]inositol for 90 min. The amounts of inositol phospholipids in liver plasma membranes (in micrograms/mg protein) were 2.1 +/- 0.2 for PIP2, 0.24 +/- 0.03 for PIP, and 23 +/- 4 for PI. Comparison of these values with those for whole cells suggests that PIP2 is enriched in the plasma membrane, whereas PIP is present elsewhere in the cell. The fatty acid composition of whole cell PIP2 showed significant differences from that of PI. The percentages of palmitic, stearic, linoleic, and arachidonic acids were, respectively, 14, 41, 10, and 25 for PIP2 and 10, 34, 7, and 37 for PI. Vasopressin treatment for 15 s did not alter the fatty acid composition of PIP2. The corresponding fatty acid percentages for liver plasma membranes were 13, 41, 11, and 21 for PIP2 and 8, 34, 0, and 40 for PI. The fatty acid composition of PIP in whole cells and plasma membranes resembled that of PIP2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Changes in the concentration and fatty acid composition of phosphoinositides induced by hormones in hepatocytes. 253 16

Arginine vasopressin (AVP) has been shown previously to enhance phosphatidylinositol (PI) turnover and mobilize calcium in the rat aortic smooth muscle cell-line (A10; ATCC CRL 1476) via the V1 receptor (Aiyar, N., Nambi, P., Stassen, F. L., and Crooke, S. T. (1986) Life Sci. 39, 37-45). Exposure of A10 cells to AVP for periods ranging from 5 min to 2 h resulted in 30-40% loss in AVP-binding sites and an inhibition of the production of inositol di- and trisphosphates and the mobilization of calcium when the cells were rechallenged by addition of AVP. We now report that during the same time course AVP induces a dose- and time-dependent decrease in labeled PI, phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate reaching a minimum after 30 min of incubation. After 2 h of exposure to AVP, the levels of labeled PI, phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate increased to a new basal level approximately 30% less than the untreated cultures. The decrease in inositol lipid labeling mediated by AVP was inhibited when the V1 antagonist SK&F 100273 was included in the incubations with AVP. No decrease was observed when the V2 agonist 1-deamino, [8-D-arginine]vasopressin was used for pretreatment of the cells. Furthermore, when PI kinase activity was measured in cell extracts from untreated and AVP-treated (2 h) cells a significant decrease (p less than 0.05) was observed in the absence, but not in the presence, of added PI in the AVP-treated cells as compared with the control cells. Thrombin also stimulates PI metabolism and calcium mobilization in these cells and brought about both a prolonged decrease in inositol lipids and inhibition of PI kinase activity. AVP pretreatment affected the release of intracellular Ca2+ induced by AVP, thrombin, and ATP, differently. The time of AVP pretreatment required to induce half-maximal inhibition of intracellular Ca2+ release in response to AVP, thrombin, and ATP was approximately 8, 24, and 30 min, respectively. Consequently, we suggest that the reduction in response to AVP with short term preincubation is due to homologous desensitization as reflected by 30-40% decrease in V1 receptors. Subsequently, a decrease in inositol lipid pools and PI kinase activity results in heterologous desensitization in response to AVP, thrombin, and ATP.
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PMID:Molecular mechanisms of homologous and heterologous desensitization mediated by vasopressin in smooth muscle cells. 253 19

Cultured human renal cortical epithelial cells (NHK-C) were examined for functional and morphologic characteristics of the proximal tubule. Cultures were established by using cells isolated by progressive enzymatic dissociation from the extreme outer cortex of the normal human kidney. Cells were subcultured and used at passages 3 through 8. Cell uptake of alpha-methyl-D-glucoside (AMG), inorganic phosphate (Pi) and L-alanine was found to be dependent on the presence of Na+ in the incubation medium, and uptake increased with incubation time up to 30 minutes. Na+-dependent AMG uptake was inhibited 67% by phlorizin (1 mmol/L), and Pi uptake was inhibited 89% by parathyroid hormone (PTH) (10(-6) mol/L). Intracellular cyclic adenosine monophosphate was increased 28-fold after exposure to 10(-6) mol/L PTH but was increased only 2-fold by the same concentration of vasopressin. The cells exhibited endocytotic activity and possessed maltase, leucine aminopeptidase, and gamma-glutamyltranspeptidase, enzymes located exclusively in the brush border membranes of proximal tubule cells. NHK-C cultures were structurally heterogeneous, made up of a mixed-cell population with predominant epithelial-like morphology. Epithelial cells had cuboidal form, solitary cilia, and short, irregularly distributed apical microvilli. These cultures also formed multicellular hemicysts, but only through passage 3. NHK-C cultures showed a dramatic attenuation of proliferative activity at passages 8 through 10. These data show that subcultured cells derived from the outer cortex of the normal human kidney retain a number of functional characteristics typical of the proximal tubule.
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PMID:Proximal tubule characteristics of cultured human renal cortex epithelium. 253 26

Isolated rat hepatocytes in primary monolayer culture were maintained for 18-24 h in the presence of 10% (v/v) serum and [3H]inositol. Vasopressin (100 nM) stimulated the production of inositol mono-, bis- and tris-phosphates (IP1, IP2, and IP3). Prior exposure of hepatocytes to 8-bromo cyclic AMP (8Br-cAMP; 100 microM), but not 8-bromo cyclic GMP, enhanced the vasopressin-mediated stimulation of inositol phosphate accumulation, but had no significant effect on their formation in the absence of vasopressin. The effect of the cyclic AMP analogue was mimicked by glucagon (10 nM), and was seen whether cyclic AMP or glucagon was added 5 min or 12 h before the addition of vasopressin. An 8 h incubation with dexamethasone (100 nM) enhanced the accumulation of IP3, but not that of IP2 or IP1, in the presence of 8Br-cAMP and vasopressin. Cycloheximide or actinomycin D had little effect on the vasopressin stimulation of inositol phosphate accumulation, after an 8 h incubation in the presence or absence of 8Br-cAMP.
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PMID:Exposure of cultured hepatocytes to cyclic AMP enhances the vasopressin-mediated stimulation of inositol phosphate production. 253 87


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