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)

Glucagon was added to isolated rat hepatocytes, either alone or together with vasopressin or angiotensin II, and the effects on the initial 45Ca2+ uptake rate were investigated. Addition of glucagon alone which increased cyclic AMP content of the cells slightly increased the initial 45Ca2+ uptake rate. When glucagon was added together with vasopressin or angiotensin II--both of which when added separately increase the initial 45Ca2+ uptake rate but did not affect the cellular content of cyclic AMP--the measured initial 45Ca2+ uptake rate was larger than the sum of that seen with each hormone alone. This indicates that glucagon and Ca2+-linked hormones synergistically enhanced the Ca2+ influx in rat hepatocytes. These effects of glucagon can be mimicked by dibutyryl cyclic AMP or forskolin, suggesting that cyclic AMP augments both the resting Ca2+ and the vasopressin- or angiotensin II-stimulated influx. Measurement of the initial 45Ca2+ uptake rate as a function of the extracellular Ca2+ concentration indicated that the increase in the Ca2+ influx resulting from single or combined glucagon and vasopressin administration occurred through a homogeneous population of Ca2+ gates. These hormones were found to raise both the apparent Km for external Ca2+ and the apparent Vmax of the Ca2+ influx. The maximal increase in these two parameters was observed when the two hormones were added together. This suggests that glucagon and vasopressin synergistically stimulate the same Ca2+ gating mechanism. The dose-response curves for the action of glucagon or vasopressin applied in the presence of increasing concentrations of vasopressin or glucagon, respectively, showed that each hormone increases the maximal response to the other without affecting its ED50. It is proposed that glucagon and the Ca2+-linked hormones control the cellular concentration of two intermediates which are both necessary to allow Ca2+ entry into the cells.
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PMID:Synergistic stimulation of the Ca2+ influx in rat hepatocytes by glucagon and the Ca2+-linked hormones vasopressin and angiotensin II. 299 43

The effects of hormones on the cytochrome spectra of isolated hepatocytes were recorded under conditions of active gluconeogenesis from L-lactate. Glucagon, phenylephrine, vasopressin and valinomycin, at concentrations that caused stimulation of gluconeogenesis, increased the reduction of the components of the cytochrome bc1 complex, just as has been observed in liver mitochondria isolated from glucagon-treated rats [Halestrap (1982) Biochem. J. 204, 37-47]. The effects of glucagon and phenylephrine were additive. The time courses of the increased reduction of cytochrome c/c1 and NAD(P)H/NAD(P)+ caused by hormones, valinomycin, A23187 and ethanol were measured by dual-beam spectrophotometry and fluorescence respectively. Ethanol (14 mM) produced a substantial rise in NAD(P)H fluorescence, beta-hydroxybutyrate/acetoacetate and lactate/pyruvate ratios, no change in cytochrome c/c1 reduction, a 10% decrease in O2 consumption and a 60% decrease in gluconeogenesis. Glucagon, phenylephrine and vasopressin caused a substantial and transient rise in NAD(P)H fluorescence, but a sustained increase in cytochrome c/c1 reduction and the rates of O2 consumption and gluconeogenesis. The transience of the fluorescence response was greater in the absence of Ca2+, when the cytochrome c/c1 response also became transient. The fluorescence response was smaller and less transient, but the cytochrome c/c1 response was greater, in the presence of fatty acids. Both responses were greatly decreased by the presence of 1 mM-pent-4-enoate. Valinomycin (2.5 nM) caused a decrease in NAD(P)H fluorescence coincident with an increase in cytochrome c/c1 reduction and the rate of gluconeogenesis and O2 consumption. A23187 (7.5 mM) caused increases in both NAD(P)H fluorescence and cytochrome c/c1 reduction. The effects of hormones and valinomycin on the time courses of NAD(P)H fluorescence, cytochrome c/c1 reduction and light-scattering by hepatocytes were compared with those of 0.5 microM-Ca2+ or 1 nM-valinomycin on the same parameters of isolated liver mitochondria. It is concluded that hormones increase respiration by hepatocytes in a biphasic manner. An initial Ca2+-dependent activation of mitochondrial dehydrogenases rapidly increases the mitochondrial [NADH], which is followed by a volume-mediated stimulation of fatty acid oxidation and electron flow between NADH and cytochrome c. 10. Amytal (0.5 mM) was able to reverse the effects of hormones on the reduction of cytochromes c/c1 and the rates of gluconeogenesis and O2 consumption without significantly lowering tissue [ATP].(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The mechanism of the hormonal activation of respiration in isolated hepatocytes and its importance in the regulation of gluconeogenesis. 302 26

The effects of propylthiouracil (PTU) treatment on vasopressin, angiotensin II, glucagon and alpha 1-adrenergic receptors in both developing and adult rats were studied in liver membrane preparations by measuring the binding of the following ligands: [3H][8-lysine]vasopressin, [3H]Sar-angiotensin II, [125I]glucagon and [3H]prazosin, and in the case of glucagon, by measuring adenylate cyclase activation. Whatever the ligand used, in young as well as in adult animals, PTU treatment led to a similar reduction (about 50%) in the maximal number of binding sites (Bmax), without significant changes in the apparent dissociation constant (KD) of labeled hormone for its specific receptor. In normal adult animals, thyroxine treatment, i.e. hyperthyroidism, had an opposite effect on the Bmax (25-50% increase), without changes in the KD. In developing PTU-treated rats, the abnormalities completely disappeared after therapy with increasing physiological doses of thyroxine; consequently they were directly related to thyroid deficiency and not to toxic effects of PTU. Moreover, the abnormalities resulting from induced hypothyroidism were reversible. In developing and adult hypothyroid rats, neither basal, NaF-, nor Gpp(NH)p-stimulated adenylate cyclase activities were significantly affected. Glucagon-sensitive adenylate cyclase activity seemed to be slightly increased (by about 15%), without changes in the apparent activation constant (Kact). These results are considered in parallel with findings on plasmatic glucagon and vasopressin levels, compared with similar previous reports related to renal vasopressin receptors, and discussed with respect to unpublished observations concerning hepatic responsiveness to glycogenolytic hormones in young and adult rats with induced hypothyroidism.
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PMID:Comparative study of the developmental patterns of vasopressin, glucagon, angiotensin II, and alpha 1-adrenergic receptors in the liver of developing and adult hypothyroid rats. 303 20

Treatment of intact hepatocytes with glucagon, TH-glucagon [( 1-N-alpha-trinitrophenylhistidine, 12-homoarginine]glucagon), angiotensin or vasopressin led to a rapid time- and dose-dependent loss of the glucagon-stimulated response of the adenylate cyclase activity seen in membrane fractions isolated from these cells. Intracellular cyclic AMP concentrations were only elevated with glucagon. All ligands were capable of causing both desensitization/loss of glucagon-stimulated adenylate cyclase activity and stimulation of inositol phospholipid metabolism in the intact hepatocytes. Maximally effective doses of angiotensin precluded any further inhibition/desensitizing action when either glucagon or TH-glucagon was subsequently added to these intact cells, as has been shown previously for the phorbol ester TPA (12-O-tetradecanoylphorbol 13-acetate) [Heyworth, Wilson, Gawler & Houslay (1985) FEBS Lett. 187, 196-200]. Treatment of intact hepatocytes with these various ligands caused a selective loss of the glucagon-stimulated adenylate cyclase activity in a washed membrane fraction and did not alter the basal, GTP-, NaF- and forskolin-stimulated responses. Angiotensin failed to inhibit glucagon-stimulated adenylate cyclase activity when added directly to a washed membrane fraction from control cells. Glucagon GR2 receptor-stimulated adenylate cyclase is suggested to undergo desensitization/uncoupling through a cyclic AMP-independent process, which involves the stimulation of inositol phospholipid metabolism by glucagon acting through GR1 receptors. This action can be mimicked by other hormones which act on the liver to stimulate inositol phospholipid metabolism. As the phorbol ester TPA also mimics this process, it is proposed that protein kinase C activation plays a pivotal role in the molecular mechanism of desensitization of glucagon-stimulated adenylate cyclase. The site of the lesion in desensitization is shown to be at the level of coupling between the glucagon receptor and the stimulatory guanine nucleotide regulatory protein Gs, and it is suggested that one or both of these components may provide a target for phosphorylation by protein kinase C.
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PMID:The rapid desensitization of glucagon-stimulated adenylate cyclase is a cyclic AMP-independent process that can be mimicked by hormones which stimulate inositol phospholipid metabolism. 303 85

The effect of gastric secretory inhibitors, vasoactive agents and gastrointestinal peptide hormones were investigated on gastric mucosal blood flow (MBF) and HCl secretion in 197 subjects. Changes in MBF were estimated by a new clearance substance, 99mTc-4-methyl-aminophenazone originally described by the authors. The procedure seemed to be suitable for characterizing changes in MBF without any toxic side effect or considerable radioactive loading of the patient or its surroundings. The studies were performed after a secretory steady state had been achieved by continuous pentagastrin infusion. Some experiments were done in the fasting stomach instilled with 0.160 N HCl. Secretory inhibition following atropine, pirenzepine, ranitidine and somatostatin was a primary effect of these substances, the observed MBF decrease being a secondary one. In contrast, vasopressin caused a fall in mucosal blood supply through vasoconstriction, the concomitant secretory inhibition being a secondary phenomenon. Certain doses of dopamine and terbutaline increased MBF without influencing HCl secretion. Glucagon in the dose used did not influence either mucosal blood flow or acid secretion. Synthetic secretin in the fasting stomach increased MBF without affecting HCl production; during pentagastrin stimulation it inhibited acid production while MBF remained unchanged. Cholecystokinin-octapeptide proved to be a direct vasodilating agent with a slight acid output increasing effect. Divergent effects of some drugs on mucosal blood flow and HCl production may be important in the pathology of hypoxic ulcerative damage and in the reparative processes of gastric ulceration. The 99mTc-4-methyl-aminophenazone clearance technique proved to be a reliable method for screening of drugs possessing vasoactive or secretion influencing properties.
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PMID:Mucosal blood flow changes in the human stomach measured by the 99mTc-4-methylaminophenazone clearance technique. 368 45

The regulatory mechanism of hepatic palmitate oxidation into ketone bodies by c-kinase has been studied in isolated hepatocytes. Glucagon and epinephrine stimulated [U-14C]palmitate oxidation to ketone bodies by 60 and 25% as early as at 1 h. The stimulatory effects were almost totally prevented by the simultaneous presence of vasopressin, phorbol 12-tetradecanoate 13-acetate (TPA), or diacylglycerol (1-oleoyl-2-acetylglycerol). When hepatocytes were treated with glucagon or epinephrine, carnitine palmitoyltransferase (CPT), a key regulatory enzyme of palmitate oxidation, was activated. This hormone-induced activation of CPT was not observed in the presence of TPA. These observations suggest that c-kinase inhibits glucagon- or epinephrine-stimulated palmitate oxidation to ketone bodies, and that this inhibition may be mediated through a covalent modification of CPT.
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PMID:A suppressive role of c-kinase for the stimulation of hepatic ketogenesis by glucagon and epinephrine. 370 11

The effect of acetylglyceryl ether phosphorylcholine (AGEPC) on glycogenolysis and phosphatidylinositol 4,5-bisphosphate has been studied in rat hepatocytes. Previously, this laboratory demonstrated that AGEPC stimulated glucose output from the perfused rat liver and promoted the breakdown of phosphoinositides in rat hepatocytes (Shukla, S. D., Buxton, D. B., Olson, M.S., and Hanahan, D.J. (1983) J. Biol. Chem. 258, 10212-10214). In the present study, addition of AGEPC (10(-13) to 10(-9) M) to rat hepatocytes failed to stimulate glucose output, whereas epinephrine (10(-5)M) and glucagon (10(-7)M) stimulated glucose output by 100% or more in these same cells. The effects of AGEPC, epinephrine, vasopressin, and glucagon on glycogen phosphorylase activity and the breakdown of phosphatidylinositol 4,5-bisphosphate were compared in hepatocytes. AGEPC (10(-9)M) promoted the breakdown of phosphatidylinositol 4,5-bisphosphate in a fashion similar to epinephrine (10(-5)M) and vasopressin (10(-7)M). In contrast to the two calcium-mobilizing hormones, epinephrine and vasopressin, AGEPC did not cause an activation of glycogen phosphorylase. Glucagon activation of glycogen phosphorylase was not accompanied by a significant effect on phosphatidylinositol 4,5-bisphosphate hydrolysis. Thus, AGEPC is a chemical mediator which induces the degradation of phosphatidylinositol 4,5-bisphosphate without activating glycogenolysis in hepatocytes.
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PMID:The effect of acetylglyceryl ether phosphorylcholine on glycogenolysis and phosphatidylinositol 4,5-bisphosphate metabolism in rat hepatocytes. 608 6

Glucagon is able to diminish the net release of inorganic phosphate (Pi) occurring on incubation of isolated hepatocytes from 48-h-starved rats. Concomitantly the hormone increases the cellular Pi content. This is associated with a rise of Pi in the cytosolic fraction. Other hormonal effectors like phenylephrine, vasopressin and angiotensin II exert a smaller and transient effect as compared to glucagon. It is proposed that this increase in Pi availability to the mitochondria, by favouring substrate level phosphorylation at the succinyl-CoA synthetase step plays a role in the development of the metabolite pattern found in the mitochondrial matrix space after exposure of hepatocytes to glucagon or the above agents. With regard to the glutamate level this view is evidenced by the finding that its hormone-dependent decrease was inversely correlated to the respective increase in the cytosolic Pi concentration. Further evidence is provided by experiments with isolated mitochondria incubated under state-3 conditions at medium Pi concentrations corresponding to those metabolically active in the cytosolic compartment of control and glucagon-stimulated hepatocytes, being 2 mM and 3 mM, respectively. Increasing medium phosphate concentration from 2 mM to 3 mM caused a marked decrease in the level of succinyl-CoA and increased the rates of 2-oxoglutarate utilization and of malate and phosphoenolpyruvate production. Citrulline synthesis also was found to be stimulated at 3 mM Pi. Taken together our results suggest a role of Pi supply in mitochondrial actions of glucagon in intact hepatocytes. Moreover, they could contribute to a better interpretation of glucagon effects on isolated mitochondria from hormone-pretreated liver cells.
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PMID:Possible role of Pi supply in mitochondrial actions of glucagon. 614 21

Isolated rat hepatocytes in primary culture were used as a model system to evaluate the effects of selected hormones and culture conditions on the efflux of calcium-45 and lead-210 from cells labeled with these isotopes. Alpha-adrenergic stimuli, angiotensin, vasopressin, dibutyryl adenosine 3',5'-monophosphate, and reduced phosphate concentrations in the medium increased the efflux of calcium-45 and lead-210. Glucagon and insulin had no effect, but increased phosphate concentrations decreased the efflux of both isotopes. Experiments with hepatocytes cultured in a medium free of calcium and lead demonstrated that the increased efflux of calcium-45 and lead-210 induced by hormones was the result of mobilization of the ions from intracellular stores. The data indicate that the physiological stimuli that mobilized calcium ions also mobilized lead ions, and that the mobilized lead would be available to interact with calcium-mediated cell functions.
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PMID:Mobilization of cellular calcium-45 and lead-210: effect of physiological stimuli. 630 Oct 3

Exposure of 32P-prelabelled isolated hepatocytes to vasopressin affected the phosphorylation of nine of the 26 phosphoproteins resolved by sodium dodecyl sulphate gel electrophoresis. Glucagon (2 nM) or cyclic AMP elicited significant changes in the phosphorylation of only four phosphoproteins. A very high concentration of glucagon (1000 nM) affected additional phosphoproteins. Insulin alone significantly increased the phosphorylation of a single protein. Vasopressin, A23187, glucagon and cyclic AMP all induced the dephosphorylation of a single phosphoprotein of mol. wt 20,000. The significance of these results with respect to the short-term control of hepatic metabolism is discussed.
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PMID:The short term hormonal control of cytoplasmic protein phosphorylation in hepatocytes from fed rats. 635 57

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