UNIPROT:P01185 - FACTA Search

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

Rats were treated with Escherichia coli endotoxin (ET) either acutely or chronically or rendered septic by cecal ligation and puncture. At 6 h after ET injection, at various intervals of continuous ET infusion, and at 17-18 h after the onset of peritonitis, animals were killed and hepatocytes were isolated. Cytosolic [Ca2+] ([Ca2+]c) was measured by quin 2 during the resting state and after stimulation with epinephrine and vasopressin. Basal and epinephrine-, vasopressin- and glucagon-stimulated glycogen phosphorylase activity were also determined. In hepatocytes from acutely ET-treated rats, resting levels of [Ca2+]c were decreased 46% from 245.8 +/- 11.0 to 131.0 +/- 8.5 nM (n = 4-6, P less than 0.05). In septic rats a 39.5% decrease was noted [i.e., from 154.0 +/- 17.7 (n = 4, sham) to 93.3 +/- 91 nM (n = 5, septic, P less than 0.05)]. These decreased [Ca2+]c levels were associated with changes of glycogen phosphorylase activity in a manner suggesting a cause and effect relationship; e.g., acute ET treatment resulted in greater than 80% depression of phosphorylase a activity, whereas sepsis induced a 58% decrease in the activity of this enzyme. In ET-infused rats the resting level of [Ca2+]c and its response to hormonal stimulation were not different from hepatocytes of saline-infused rats, although glycogen phosphorylase activity was less responsive to these hormones. The effect on the enzyme's response to Ca2+-mobilizing hormones was more marked than to glucagon. This is consistent with the concept that information flow in the Ca2+-messenger system is a site of metabolic lesions produced by endotoxicosis and sepsis.
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PMID:Rat liver free cytosolic Ca2+ and glycogen phosphorylase in endotoxicosis and sepsis. 353 41

Arginine vasotocin (AVT) caused a concentration-dependent increase of glycogen phosphorylase alpha activity, breakdown of glycogen and release of glucose, when added to pieces of axolotl liver in organ culture. The concentration causing half-maximal response (EC50) was about 1 nmol/l. These actions of AVT were unaffected by the adrenergic antagonists propranolol, yohimbine and prazosin, but were blocked by equimolar amounts of d(CH2)5Tyr(Me)AVT, a synthetic antagonist of vasopressin. Arginine vasotocin similarly caused glycogenolysis in isolated perfused axolotl liver where the EC50 was about 0.1 nmol/l. The glycogenolytic action of AVT (10 nmol/l) was sustained for at least 3 h in Ca2+-free perfusion and longer in organ culture. No increase in Ca2+ concentration in the effluent perfusion medium was apparent during AVT-induced glucose release. Omission of Ca2+ from the medium, together with addition of EGTA (2.5 mmol/l) to the organ culture, had only a slight inhibitory effect upon the rate of glycogenolysis brought about by AVT and did not inhibit the glycogenolytic action of catecholamines. Addition of the calcium ionophore A23187 (5 mumol/l) neither caused glucose release nor abolished the glycogenolytic action of AVT added subsequently. Nevertheless, A23187 caused increased loss of 45Ca from Ca2+-loaded liver pieces whereas AVT was without effect. There was a slight accumulation of cyclic AMP (cAMP), but not cGMP, in axolotl liver pieces cultured in the presence of 0.1 mumol AVT/l and this was accentuated in the presence of phosphodiesterase inhibitors. We conclude that, in contrast to the position in mammals, Ca2+ is not involved in the glycogenolytic actions of AVT or catecholamines in axolotl liver. Preliminary experiments suggest that the same is true in the carp and we suggest that the involvement of Ca2+ in regulation of hepatic glucose release may not have evolved until after the amphibians separated from the ancestors of the mammals.
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PMID:Calcium-independent stimulation of glycogenolysis by arginine vasotocin and catecholamines in liver of the axolotl (Ambystoma mexicanum) in vitro. 370 Dec 46

Isolated hepatocytes from fed rats were used to study the effects of the opioid peptide [Leu]enkephalin on intracellular free cytosolic Ca2+ ([Ca2+]i) and inositol phosphate production. By measuring the fluorescence of the intracellular Ca2+-selective indicator quin-2, [Leu]enkephalin was found to increase [Ca2+]i rapidly from a resting value of 0.219 microM to 0.55 microM. The magnitude of this response was comparable with that produced by maximally stimulating concentrations of either vasopressin (100 nM) or phenylephrine (10 microM). The opioid-peptide-mediated increase in [Ca2+]i showed a dose-dependency comparable with the activation of phosphorylase, but it preceded the increase in phosphorylase alpha activity. Addition of [Leu]enkephalin to hepatocytes prelabelled with myo-[2-3H(n)]inositol resulted in a significant stimulation of inositol phosphate production. At 10 min after hormone addition, there were increases in the concentrations of inositol mono-, bis- and tris-phosphate fractions of 12-, 9- and 14-fold respectively. No effect was apparent on the glycerophosphoinositol fraction. The effect of 10 microM-[Leu]enkephalin on inositol phosphate production was significantly greater than that obtained with 10 microM-phenylephrine, but marginally smaller than that induced by 100 nM-vasopressin. However, at these concentrations all three agonists gave a comparable increase in [Ca2+]i and activation of phosphorylase a. These data provide evidence for [Leu]enkephalin acting via a mechanism involving a mobilization of Ca2+ as a result of increased phosphatidylinositol turnover.
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PMID:Changes in free cytosolic calcium and accumulation of inositol phosphates in isolated hepatocytes by [Leu]enkephalin. 380 Sep 50

At maximally effective concentrations, vasopressin (10(-7) M) increased myo-inositol trisphosphate (IP3) in isolated rat hepatocytes by 100% at 3 s and 150% at 6 s, while adrenaline (epinephrine) (10(-5) M) produced a 17% increase at 3 s and a 30% increase at 6 s. These increases were maintained for at least 10 min. Both agents increased cytosolic free Ca2+ [( Ca2+]i) maximally by 5 s. Increases in IP3 were also observed with angiotensin II and ATP, but not with glucagon or platelet-activating factor. The dose-responses of vasopressin and adrenaline on phosphorylase and [Ca2+]i showed a close correspondence, whereas IP3 accumulation was 20-30-fold less sensitive. However, significant (20%) increases in IP3 could be observed with 10(-9) M-vasopressin and 10(-7) M-adrenaline, which induce near-maximal phosphorylase activation. Vasopressin-induced accumulation of IP3 was potentiated by 10mM-Li+, after a lag of approx. 1 min. However the rise in [Ca2+]i and phosphorylase activation were not potentiated at any time examined. Similar data were obtained with adrenaline as agonist. Lowering the extracellular Ca2+ to 30 microM or 250 microM did not affect the initial rise in [Ca2+]i with vasopressin but resulted in a rapid decline in [Ca2+]i. Brief chelation of extracellular Ca2+ for times up to 4 min also did not impair the rate or magnitude of the increase in [Ca2+]i or phosphorylase a induced by vasopressin. The following conclusions are drawn from these studies. IP3 is increased in rat hepatocytes by vasopressin, adrenaline, angiotensin II and ATP. The temporal relationships of its accumulation to the increases in [Ca2+]i and phosphorylase a are consistent with it playing a second message role. Influx of extracellular Ca2+ is not required for the initial rise in [Ca2+]i induced by these agonists, but is required for the maintenance of the elevated [Ca2+]i.
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PMID:Stimulation of inositol trisphosphate formation in hepatocytes by vasopressin, adrenaline and angiotensin II and its relationship to changes in cytosolic free Ca2+. 387 38

Experiments were carried out to investigate the role of extracellular phosphate in the hormonal regulation of glycogenolysis in perfused fed-rat liver. Omission of phosphate from the perfusate did not affect the ATP, ADP and AMP contents of the tissue and the basal glucose output from the perfused liver. However, it inhibited significantly the glycogenolysis induced by glucagon, cyclic AMP, phenylephrine and vasopressin but not that induced by 2,4-dinitrophenol. In the absence of perfusate phosphate, the increase in phosphorylase a activity caused by the addition of glucagon, phenylephrine and vasopressin was significantly less than that observed in the presence of perfusate phosphate. Insulin inhibition of the glucagon- or cyclic AMP-induced glycogenolysis was abolished when the perfusion was carried out with the phosphate-free buffer. However, the inhibitory effect of insulin on phenylephrine-induced glycogenolysis was clearly demonstrated even when the perfusate contained no phosphate. These data indicate that in the phosphate-depleted liver, the hormonal control of phosphorylation and dephosphorylation of phosphorylase is impaired. The difference in the phosphate dependency of insulin action on glucagon-and alpha-adrenergic agonist-induced glycogenolysis suggests that the mechanism or site of insulin action on glucagon and phenylephrine is different.
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PMID:Influence of extracellular phosphate concentrations on the regulation of hepatic glucose output. 389 90

Receptor-mediated breakdown of PtdIns(4,5)P2 produces two cellular signals, Ins(1,4,5)P3, which can release intracellular Ca2+, and diacylglycerol, which activates a Ca2+- and phospholipid-dependent protein kinase (protein kinase C). This study assesses the significance of protein kinase C in relation to phenylephrine- and vasopressin-induced Ca2+ mobilization in hepatocytes. Phorbol ester (4 beta-phorbol-12-myristate-13-acetate), which can directly activate protein kinase C, had no effect either on Ca2+ efflux from the cell (measured with arsenazo III) or on Ca2+ influx (measured with Quin-2), processes which are inhibited and stimulated, respectively, by both phenylephrine and vasopressin. No evidence of synergism between phorbol ester pretreatment of hepatocytes and the Ca2+ ionophore (ionomycin)-mediated effects on the increase of cytosolic free Ca2+ and phosphorylase activation could be obtained. These findings suggest that protein kinase C is not obligatorily involved in the regulation of hepatocyte Ca2+ fluxes. Pretreatment of hepatocytes with phorbol ester (PMA) or 1-oleoyl-2-acetylglycerol totally inhibited the effects of phenylephrine in elevating the cytosolic free Ca2+; half-maximal inhibitory effects occurred at PMA and 1-oleoyl-2-acetylglycerol concentrations of 1 ng/ml and 12 micrograms/ml, respectively. In contrast, pretreatment with PMA had a much smaller effect on Ca2+ mobilization induced by vasopressin. These observations suggest that protein kinase C may be involved in "down-regulation" of the alpha 1-receptor in hepatocytes and may thus exert a negative influence on the Ca2+-signalling pathway.
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PMID:Differential effects of phorbol ester on phenylephrine and vasopressin-induced Ca2+ mobilization in isolated hepatocytes. 391 20

1,2-Diacylglycerol (DAG) was measured in neutral lipid extracts from isolated hepatocytes using high pressure liquid chromatography followed by refractive index detection. Maximally effective doses of epinephrine, angiotensin II, and vasopressin increased DAG by approximately 65, 80, and 180-250%, respectively, with maximal increases being observed at 8-10 min. Depletion of cellular Ca2+ resulted in a 50% decrease in DAG accumulation elicited by vasopressin. Other agents which increased DAG levels were the tumor promoter 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (120% increase at 10(-6) M), the Ca2+ ionophore A23187 (385% increase at 10(-5) M), and ATP (180% increase at 1 mM). The concentration dependence of DAG accumulation in response to epinephrine, angiotensin II, and vasopressin was similar to that found for myoinositol triphosphate accumulation (Charest, R., Prpic, V., Exton, J. H., and Blackmore, P.F. (1985) Biochem. J. 227, 79-90), which was approximately 5-10 times less sensitive to hormone than was phosphorylase activation. Fatty acid analysis revealed that hormonally induced DAG was partially derived from sources other than inositol phospholipids. It is proposed from these studies that Ca2+-mobilizing hormones elicit a prolonged increase in the levels of hepatocyte DAG, which may activate protein kinase C.
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PMID:Stimulation of 1,2-diacylglycerol accumulation in hepatocytes by vasopressin, epinephrine, and angiotensin II. 393 51

In isolated rat hepatocytes: phosphorylase activation by the ionophore A23187 was enhanced in the presence of tumour-promoting phorbol esters and 1,2- (but not 1,3-) diacylglycerols (dioleoyl- and oleoylacetyl-glycerol), with a similar dose-dependency; the activation of phosphorylase by phenylephrine (1 microM) (but not by vasopressin or glucagon) was inhibited both by tumour-promoting phorbol esters and diacylglycerols, but with a different dose-dependency: complete inhibition was achieved with concentrations of phorbol esters two orders of magnitude lower than those of diacylglycerol; binding of the alpha 1-adrenergic antagonist [3H]prazosin and its displacement by unlabelled prazosin was not significantly affected in the presence of the phorbol esters. The possible involvement of protein kinase C in the control of phosphorylase interconversion is discussed.
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PMID:Control of glycogen phosphorylase interconversion by phorbol esters, diacylglycerols, Ca2+ and hormones in isolated rat hepatocytes. 393 4

The role of extracellular calcium in hormone-induced glycogenolysis was examined in a rat liver perfusion system by manipulating the perfusate calcium concentration and by using calcium antagonistic drugs. When the perfusate contained 1 mM CaCl2, 5 microM phenylephrine, 20 nM vasopressin, and 10 nM angiotensin II caused a persistent increase in glucose output and phosphorylase activity as well as a transient increase in 45Ca efflux from 45Ca preloaded liver. Verapamil hydrochloride (20-100 microM) inhibited the activation of glucose output by these hormones in a dose-dependent manner. This inhibitory effect was also associated with the inhibition of hormone-induced activation of phosphorylase and 45Ca efflux. In the absence of CaCl2 in the perfusate, the glycogenolytic effect of phenylephrine and its inhibition by verapamil were obtained equally as in the presence of CaCl2. However, the effects of vasopressin and angiotensin II were markedly attenuated and were not inhibited any further by verapamil. The substitution of diltiazem hydrochloride for verapamil produced essentially identical results. Cyclic AMP concentrations in the tissue did not change under any of these test conditions. The results indicate that the glycogenolytic effect of alpha-adrenergic agonists depends on intracellular calcium but those of vasopressin and angiotensin II on extracellular calcium, and support the concept that calcium antagonistic drugs inhibit the glycogenolytic effects of calcium-dependent hormones at least by inhibiting the mobilization of calcium ion from cellular pools.
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PMID:Difference in the mechanism of action of alpha-adrenergic agonists and vasopressin or angiotensin II in stimulating hepatic glycogenolysis; a role of extracellular calcium concentration. 401 69

The action of alpha 1-adrenergic agonists (noradrenaline in the presence of propranolol), vasopressin and angiotensin on the intracellular free Ca2+ concentration, [Ca2+]i, was determined by using the fluorescent dye quin2 in isolated rat liver cells. In the presence of external Ca2+ (1.8 mM), 1 microM-noradrenaline induced an increase in [Ca2+]i up to about 800 nM without apparent delay, whereas 10 nM-vasopressin and 1 nM-angiotensin increased [Ca2+]i to values higher than 1500 nM with a lag period of about 6s. The successive addition of the hormones and of their specific antagonists indicated that the actions of the three Ca2+-mobilizing hormones occurred without apparent desensitization (over 6 min) and via independent receptors. The relative contributions of internal and external Ca2+ pools to the cell response were determined by studying the hormone-mediated [Ca2+]i increase and glycogen phosphorylase activation in low-Ca2+ media (22 microM). In this medium: (1) [Ca2+]i was lowered and the hormones initiated a transient instead of a sustained increase in [Ca2+]i; subsequent addition (2 min) of a second hormone promoted a lesser increase in [Ca2+]i; in contrast, the subsequent addition (2 min) of Ca2+ (1.8 mM) caused [Ca2+]i to increase to a value close to that initiated by the hormone in control conditions, the amplitude of the latter response being dependent on the concentration of Ca2+ added to the medium; (2) returning to normal Ca2+ (1.8 mM) restored the resting [Ca2+]i and allowed the hormone added 2 min later to promote a large increase in [Ca2+]i whose final amplitude was also dependent on the concentration of Ca2+ added beforehand. Similar results were found when the same protocol was applied to the glycogen phosphorylase activation. It is concluded that Ca2+ influx is required for a maximal and sustained response and to reload the hormone-sensitive stores.
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PMID:Hormone-induced increase in free cytosolic calcium and glycogen phosphorylase activation in rat hepatocytes incubated in normal and low-calcium media. 402 98

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