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)

The activation of phosphoinositide-specific phospholipase C by ethanol was compared in hepatocytes isolated from ethanol-fed rats and from pair-fed control animals. Ethanol (100-300 mM) caused a dose-dependent transient increase in cytosolic free Ca2+ levels in indo-1-loaded hepatocytes from both groups of animals. The rate of Ca2+ increase was similar in hepatocytes from control and ethanol-fed rats, but the decay of the Ca2+ increase was somewhat slower in the latter preparation. The ethanol-induced Ca2+ increase caused activation of glycogen phosphorylase, with 50% response at 50 mM-ethanol and a maximal response at 150-200 mM-ethanol, not significantly different in hepatocytes from control and ethanol-fed animals. Ins(1,4,5)P3 formation in response to ethanol (300 mM) or vasopressin (2 nM or 40 nM) was also similar in the two preparations. It is concluded that long-term ethanol feeding does not lead to an adaptive response with respect to the ethanol-induced phospholipase C activation in rat hepatocytes. The ability of ethanol in vitro to decrease membrane molecular order in liver plasma membranes from ethanol-fed and control rats was measured by e.s.r. Membranes from ethanol-fed animals had a significantly lower baseline order parameter compared with control preparations (0.313 and 0.327 respectively), indicative of decreased membrane molecular order. Addition of 100 mM-ethanol significantly decreased the order parameter in control preparations by 2.1%, but had no effect on the order parameter of plasma membranes from ethanol-fed rats, indicating that the plasma membranes had developed tolerance to ethanol, similar to other membranes in the liver. Thus the membrane structural changes associated with this membrane tolerance do not modify the ethanol-induced activation of phospholipase C. The transient activation of phospholipase C by ethanol in hepatocytes may play a role in maintaining an adaptive phenotype in rat liver.
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PMID:Phospholipase C activation by ethanol in rat hepatocytes is unaffected by chronic ethanol feeding. 217 85

Arachidonic acid (AA) is reported to be metabolized by three major pathways, i.e., cyclooxygenase (CO), lipoxygenase (LO), and NADPH-dependent cytochrome P450 monooxygenase (MO) pathways. Monooxygenase metabolites of AA have been proposed to play an important role in hormone action in various cells. Recently it was reported that the MO pathway may exist in rat liver. The present study was carried out to investigate the role of MO metabolites in vasopressin-induced glycogenolysis in isolated rat hepatocytes. The pretreatment of isolated rat hepatocytes with eicosatetraynoic acid (ETYA), an inhibitor of CO, LO, and MO pathways, and ketoconazole and SKF 525A, inhibitors of the MO pathway, dose-dependently reduced vasopressin-induced phosphorylase activation, while the pretreatment with indomethacin, an inhibitor of the CO pathway, had no effect. The increment of cytosolic calcium concentration in vasopressin-stimulated hepatocytes was also dose-dependently decreased by ETYA, ketoconazole, and SKF 525A. In vitro addition of epoxyeicosatrienoic acid (EET) dose-dependently increased both phosphorylase a activity and cytosolic calcium concentration. 14,15-EET was the most potent among four regioisomeric EETs. These results suggest that MO metabolites of AA, most likely EETs, may be involved in vasopressin-induced glycogenolysis probably via the activation of phosphorylase by increasing the cytosolic calcium concentration.
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PMID:Possible involvement of arachidonic acid metabolites of cytochrome P450 monooxygenase pathway in vasopressin-stimulated glycogenolysis in isolated rat hepatocytes. 236 26

Extracellular ATP stimulated adipocyte pyruvate dehydrogenase in a time- and dose-dependent manner with an EC50 of 0.1 mM. The maximal effect was observed at 0.5 mM ATP after a 15-min incubation with a lag period of about 5 min. Depletion of intracellular Ca2+ with ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid reduced the effect of ATP by 50% and completely abolished the stimulatory effect of vasopressin on adipocyte pyruvate dehydrogenase but had no effect on the stimulation induced by insulin or adenosine. The effects of insulin and ATP on pyruvate dehydrogenase were glucose-dependent whereas the effect of adenosine was glucose-independent. Furthermore, ATP, like insulin, partially blocked the stimulatory effect of isoproterenol on phosphorylase. Adenosine, at a concentration of 1 mM, did not affect either basal or isoproterenol-stimulated phosphorylase activities. It is concluded that ATP activates adipocyte pyruvate dehydrogenase by at least two separate mechanisms: one is Ca2(+)-dependent and the other is Ca2(+)-independent. However, neither is the result of the formation of adenosine from ATP through hydrolysis.
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PMID:Insulin-like effects of ATP on adipocyte pyruvate dehydrogenase and phosphorylase. 240 52

The effects of submaximal doses of AlF4- to mobilize hepatocyte Ca2+ were potentiated by glucagon (0.1-1 nM) and 8-p-chlorophenylthio-cAMP. A similar potentiation by glucagon of submaximal doses of vasopressin, angiotensin II, and alpha 1-adrenergic agonists has been previously shown (Morgan, N. G., Charest, R., Blackmore, P. F., and Exton, J. H. (1984) Proc. Natl. Acad. Sci. U. S. A. 81, 4208-4212). When hepatocytes were pretreated with the protein kinase C activator 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), the effects of AlF4- to mobilize Ca2+, increase myo-inositol 1,4,5-trisphosphate (IP3), and activate phosphorylase were attenuated. Treatment of hepatocytes with PMA likewise inhibits the ability of vasopressin, angiotensin II, and alpha 1-adrenergic agonists to increase IP3 and mobilize Ca2+ (Lynch, C. J., Charest, R., Bocckino, S. B., Exton, J. H., and Blackmore, P. F. (1985) J. Biol. Chem. 260, 2844-2851). In contrast, the ability of AlF4- or angiotensin II to lower cAMP or inhibit glucagon-mediated increases in cAMP was unaffected by PMA. The ability of AlF4- to lower cAMP was attenuated in hepatocytes from animals treated with islet-activating protein, whereas Ca2+ mobilization was not modified. These results suggest that the lowering of cAMP induced by AlF4- and angiotensin II was mediated by the inhibitory guanine nucleotide-binding regulatory protein of adenylate cyclase, whereas Ca2+ mobilization was not. Addition of glucagon, forskolin, or 8CPT-cAMP to hepatocytes raised IP3 and mobilized Ca2+. Both effects were blocked by PMA pretreatment, whereas cAMP and phosphorylase a levels were only minimally affected by PMA. The mobilization of Ca2+ induced by cAMP in hepatocytes incubated in low Ca2+ media was not additive with that induced by maximally effective doses of vasopressin, angiotensin II, or alpha 1-adrenergic agonists, indicating that the Ca2+ pool(s) affected by agents which increase cAMP is the same as that affected by Ca2+-mobilizing hormones which do not increase cAMP. These findings support the proposal that AlF4- mimics the effects of the Ca2+-mobilizing hormones in hepatocytes by activating a guanine nucleotide-binding regulatory protein (Np) which couples the hormone receptors to a phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phosphodiesterase. They also suggest that Np, PIP2 phosphodiesterase, or a factor involved in their interaction is activated following phosphorylation by cAMP-dependent protein kinase and inhibited after phosphorylation by protein kinase C.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Studies on the hepatic calcium-mobilizing activity of aluminum fluoride and glucagon. Modulation by cAMP and phorbol myristate acetate. 242 66

The addition of 500 microM verapamil or nifedipine to isolated hepatocytes incubated in the presence of 1.3 mM Ca2+ caused 20% inhibition of Ca2+ inflow as measured by the initial rate of 45Ca2+ exchange. No stimulation of 45Ca2+ exchange was observed in the presence of the Ca2+ agonist CGP 28392. An increase in the concentration of extracellular K+ from 6 to 60 mM (to depolarize the plasma membrane) increased the initial rate of 45Ca2+ exchange by 30%. In the presence of 60 mM K+, 400 microM verapamil inhibited the initiate rate of 45Ca2+ exchange by 50%. Verapamil and nifedipine completely inhibited vasopressin-induced Ca2+ inflow as determined by measurement of the initial rate of 45Ca2+ exchange and of glycogen phosphorylase a activity. This effect of verapamil was completely reversed by increasing the extracellular concentration of Ca2+. The concentrations of Ca2+ antagonist which gave 50% inhibition of vasopressin- or K+-stimulated Ca2+ inflow were in the range 50-100 microM, about 50-fold greater than the concentration which gave 50% inhibition of the beating of electrically-stimulated myocardial muscle cells. In the absence of vasopressin, verapamil caused a transient increase in glycogen phosphorylase a activity by a process which is largely independent of Ca2+. It is concluded that verapamil and nifedipine inhibit the transport of Ca2+ across the hepatocyte plasma membrane through a putative Ca2+ transporter which is activated by vasopressin and which differs in nature from potential-operated Ca2+ channels in excitable cells and from the Ca2+ transporter present in hepatocytes in the absence of hormone.
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PMID:Studies with verapamil and nifedipine provide evidence for the presence in the liver cell plasma membrane of two types of Ca2+ inflow transporter which are dissimilar to potential-operated Ca2+ channels. 242 76

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

We examined the effects of K+ substitution for Na+ on the response of hepatocytes to vasopressin, and on the hepatocyte plasma-membrane potential. (1) High K+ (114 mM) had no effect on the initial increase in phosphorylase a activity in response to vasopressin, but abolished the ability of the hormone to maintain increased activity beyond 10 min. With increasing concentrations a decrease in the vasopressin response was first observed at 30-50 mM-K+. (2) High K+ (114 mM) had no effect on basal 45Ca2+ influx, but abolished the ability of vasopressin to stimulate influx. This effect was also first observed at a concentration of 30-50 mM-K+. (3) Increasing K+ had little effect on the plasma-membrane potential until a concentration of 40 mM was reached. With further increases in concentration the plasma membrane was progressively depolarized. (4) Replacement of Na+ with N-methyl-D-glucamine+ depolarized the plasma membrane to a much smaller extent than did replacement with K+, and was also much less effective in inhibiting the vasopressin response. (5) The plasma-membrane potential was restored to near the control value by resuspending cells in normal-K+ medium after exposure to high-K+ medium. The effects of vasopressin on phosphorylase activity were also restored. (6) We conclude that the Ca2+ channels responsible for vasopressin-stimulated Ca2+ influx are closed by depolarization of the plasma membrane.
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PMID:Vasopressin-stimulated Ca2+ influx in rat hepatocytes is inhibited in high-K+ medium. 254 88

In rat liver prostaglandin F2 alpha (PGF2 alpha) and thromboxane A2 (TXA2), released from non-parenchymal cells, have been implicated as mediators of the enhancement of glucose and lactate output from parenchymal cells caused by sympathetic nerve stimulation [Iwai, M. et al. (1988) Eur. J. Biochem. 175, 45-50]. In isolated rat hepatocytes PGF2 alpha, of which 75% were degraded within 10 min, but not the TXA2 analogue U46619 increased inositol 1,4,5-trisphosphate (IP3), glycogen phosphorylase a activity and glucose output like noradrenaline and vasopressin; cyclic AMP remained unaltered. The maximal increase in IP3 was reached within 20 s and in phosphorylase activity as well as glucose release within 1 min. The results indicate that only PGF2 alpha but not TXA2 can play a role as a direct mediator of the sympathetic metabolic nerve actions in rat liver and that hepatocytes contain also stimulatory prostaglandin receptors linked to phospholipase C in addition to the inhibitory receptors linked to adenylate cyclase known thus far.
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PMID:Direct activation by prostaglandin F2 alpha but not thromboxane A2 of glycogenolysis via an increase in inositol 1,4,5-trisphosphate in rat hepatocytes. 255 Dec 82

The effects of diabetes on basal calcium metabolism and the response to endocrine stimulation were studied in hepatocytes from acute and long term diabetic rats. Hepatocyte calcium sequestration and turnover were increased in both acute and chronic diabetes. Cytosolic free calcium (Cai2+) was significantly increased in the chronic diabetics, but the rise in Cai2+ evoked by epinephrine, angiotensin, vasopressin, and glucagon was depressed. The blunted stimulation of phosphorylase-alpha activity in the diabetics was influenced by a 50-60% decrease in total cell activity of glycogen phosphorylase and the decreased rise in cytosolic free calcium. Insulin replacement corrected both basal and stimulated changes in the acute diabetes model. Depressed [3H]inositol trisphosphate formation in response to epinephrine or vasopressin and increased intracellular organelle calcium buffering were observed in hepatocytes from diabetic animals; both may effect the diminished rise in Cai2+. Several possible causes for the depressed rise in Cai2+ after stimulation in chronic diabetic animals were eliminated: 1) the number and affinity of alpha 1-adrenergic receptors for epinephrine were normal; 2) the initial rise in calcium influx evoked by epinephrine or vasopressin was not depressed; and 3) the ability of inositol trisphosphate to release calcium from intracellular organelles was not changed. The results suggest that the diabetic changes in calcium-mediated endocrine regulation of hepatic carbohydrate metabolism contribute to the general pathology of the disease.
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PMID:Effect of diabetes on hormone-stimulated and basal hepatocyte calcium metabolism. 255 50

The properties of the receptor-activated Ca2+ inflow system in the liver cell plasma membrane were compared with those of voltage-operated Ca2+ channels and receptor-operated Ca2+ channels present in other cell types by testing the susceptibility of the Ca2+ inflow system to inhibition by other metal ions and known inhibitors of Ca2+ movement across membranes. Co2+ inhibited Ca2+ inflow through the receptor-activated Ca2+ inflow system, as assessed by measurement of (a) the activation by extracellular Ca2+ (Cao2+) of glycogen phosphorylase in the presence of vasopressin and (b) 45Ca2+ exchange in the presence of the hormone. The concentration of Co2+ which gave half-maximal inhibition was 280 microM. The inhibition by Co2+ was reversed by high Cao2+. Co2+ did not inhibit basal Ca2+ inflow as measured by 45Ca2+ exchange in the absence of vasopressin. Zn2+, Cd2+, Ni2+ and Mn2+ each inhibited Ca2+ inflow through the receptor-activated Ca2+ inflow system. The concentrations of these ions which gave half-maximal inhibition were 10, 50, 220 and 400 microM, respectively. Little inhibition of receptor-activated Ca2+ inflow was observed in the presence of Sr2+ or Ba2+. However, substantial amounts of 90Sr2+ were taken up by hepatocytes. Rates of 90Sr2+ uptake increased from 0.5-8 nmol per min per mg wet wt. when the extracellular concentration of Sr2+ was varied from 0.25 to 2.5 mM. Sr2+ uptake was inhibited 50% by Cao2+ with half-maximal inhibition at 100 microM Cao2+, but was not inhibited by verapamil and was not stimulated by vasopressin. The movement of Ca2+ through the receptor-activated Ca2+ inflow system was not inhibited by high concentrations of each of a number of inhibitors of voltage-operated and receptor-operated Ca2+ channels and intracellular Ca2+ movement. It is concluded that while the susceptibility to inhibition by metal ions of the receptor-activated Ca2+ inflow system in the liver cell plasma membrane is similar to that of voltage-operated Ca2+ channels, there are significant differences between the liver cell receptor-activated Ca2+ inflow system and both voltage-operated Ca2+ channels and some other receptor-operated Ca2+ channels with respect to inhibition by organic compounds.
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PMID:Inhibition of the liver cell receptor-activated Ca2+ inflow system by metal ion inhibitors of voltage-operated Ca2+ channels but not by other inhibitors of Ca2+ inflow. 255 3


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