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

The quenching of fura-2 fluorescence by the influx of extracellular Mn2+ was measured to indicate the flux rates through receptor-operated calcium channels in the plasma membrane of rat hepatocytes. Neomycin, an inhibitor of phospholipase C, inhibited the vasopressin-induced influx of Mn2+. Thus, the agonist-induced entry of extracellular calcium into hepatocytes is linked to a phospholipase C-generated second messenger. Microinjection of inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4], inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] or 3-deoxy-3-fluoro-Ins(1,4,5)P3 revealed that Ins(1,4,5)P3 rather than Ins(1,3,4,5)P4 is responsible for calcium entry. The activation of phospholipase C by vasopressin produced an influx of Mn2+ independent of the depletion of intracellular calcium stores if this depletion was delayed by the Ins(1,4,5)P3 receptor antagonist heparin or by the use of a low agonist concentration. Thapsigargin, an inhibitor of the store calcium pump, leading to an Ins(1,4,5)P3-independent emptying of stores, gave a short living signal (less than 3 min) for calcium entry. We propose that Ins(1,4,5)P3 is able to stimulate calcium entry by two pathways. (a) Ins(1,4,5)P3 activates receptor-operated calcium channels in a direct manner. The calcium entry resulting from this is followed (b) by the Ins(1,4,5)P3-induced depletion of calcium stores, producing a store-dependent entry.
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PMID:Inositol 1,4,5-trisphosphate activates receptor-mediated calcium entry by two different pathways in hepatocytes. 820 Mar 48

Previous evidence has indicated a role for changes in cell membrane cholesterol in the modulation of [Ca2+]i responses and smooth muscle contraction to vascular agonists. However, the actions of plasma cholesterol-lowering agents such as 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors (eg, simvastatin) have not been defined. Such agents may in addition affect isoprenoid intermediates that may play a role in signal transduction pathways involving G proteins. Arginine vasopressin-induced [Ca2+]i responses in A10 rat vascular myocytes were therefore studied in vitro. Vasopressin stimulated an initial peak [Ca2+]i that was independent of extracellular Ca2+ entry and a subsequent plateau that was dependent on Ca2+ influx, mainly through receptor-operated dihydropyridine-insensitive divalent cation channels. Simvastatin-treated A10 cells (5 mg/L for 24 hours) showed a normal initial peak response to vasopressin, but the plateau phase of Ca2+ entry was significantly impaired. By use of Mn2+ quenching of intracellular fura 2 to measure divalent cation entry, the maximal rate of vasopressin-stimulated Mn2+ entry was impaired in simvastatin-treated cells by 52%. Mevalonate (1 mmol/L for 4 hours at 37 degrees C) reversed all the changes in simvastatin-treated cells. There were no associated changes in total cellular cholesterol or fluorescence anisotropy measurements with simvastatin treatment. Measurements of inositol-1,4,5-trisphosphate mass showed that simvastatin did not impair the initial peak response to vasopressin but significantly reduced the subsequent plateau phase. These changes were also reversed with mevalonate incubation. These findings suggest that simvastatin has additional effects on [Ca2+]i homeostasis that are independent of changes in total cell cholesterol.
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PMID:3-Hydroxy-3-methyl glutaryl coenzyme A reductase inhibition modulates vasopressin-stimulated Ca2+ responses in rat A10 vascular smooth muscle cells. 829 56

Fura-2 loaded rat hepatocytes were used to determine whether the L-type channel blockers, verapamil and diltiazem, affect receptor-operated calcium channels (ROCCs). The flux through ROCCs was followed by quenching of fura-2 fluorescence due to the influx of extracellular Mn2+ induced by vasopressin. Verapamil as well as diltiazem inhibited vasopressin-stimulated Mn2+ influx in a dose-dependent manner up to 60% at concentrations of 200-400 microM. Furthermore, both inhibitors decreased significantly the frequency of phenylephrine-induced oscillation of [Ca2+]i. The experimental findings indicate that L-type channel blockers inhibit ROCCs in rat hepatocytes.
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PMID:Verapamil and diltiazem inhibit receptor-operated calcium channels and intracellular calcium oscillations in rat hepatocytes. 838 36

Effects of genistein, a tyrosine kinase inhibitor, on increases in [Ca2+]i and protein tyrosine phosphorylation induced by 20 nM [arginine 8]vasopressin (AVP) were studied in A7r5 aortic smooth muscle cells. In fura-2-loaded cells, AVP induced a rapid (0.5-2 min) transient increase in [Ca2+]i that was followed by a smaller sustained increase in [Ca2+]i. In 66% of the cells, the transient response involved both influx of extracellular Ca2+ and release of intracellular Ca2+: influx accounted for 6% of the response, and release accounted for 40%. However, in 34% of the cells, the relative contribution of influx and release during the transient could not be assessed. In all cells, the smaller sustained response was entirely dependent on extracellular Ca2+. Genistein (148 microM) always blocked the transient and sustained components of the Ca2+ response showing that both influx and release were genistein-sensitive. Isobestic fluorescence analysis, in medium containing 0.5 mM Mn2+ in place of Ca2+, showed that the influx pathway was selective because it did not conduct Mn2+. It also confirmed that Ca2+ release was blocked by genistein. In contrast, 105 microM lavendustin A, a different tyrosine kinase inhibitor, suppressed the transient by only 30%. Another inhibitor, tyrphostin 47 (80 microM), did not alter the transient or sustained components of the Ca2+ response. No AVP-induced increases in tyrosine phosphorylation were detected unless special procedures were used. When cells were preincubated in 10 mM vanadate, a tyrosine phosphatase inhibitor, AVP induced a transient increase in tyrosine phosphorylation (5-60 s). The time course for AVP-induced phosphorylation was similar to that for increase in [Ca2+]i. Vanadate alone increased tyrosine phosphorylation and induced a slow small increase in [Ca2+]i that was dependent on extracellular Ca2+. Genistein blocked tyrosine phosphorylation induced by AVP and vanadate, and it blocked the increase in [Ca2+]i induced by vanadate alone. In contrast, lavendustin or tyrphostin unexpectedly enhanced tyrosine phosphorylation induced by vanadate alone and precluded assessment of AVP-induced tyrosine phosphorylation in the presence of vanadate. Lavendustin produced time-dependent enhancement of vanadate-induced increase in [Ca2+]i. These results underscored the need for measuring cellular changes in protein tyrosine phosphorylation to assess potential functions of tyrosine kinase activity. Under conditions where changes in phosphorylation could be measured, the results suggested that AVP-activated increases in tyrosine phosphorylation may be coupled to AVP-activated mechanisms that regulate influx of extracellular Ca2+ and release of intracellular Ca2+.
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PMID:Coupling between [arginine8]-vasopressin-activated increases in protein tyrosine phosphorylation and cellular calcium in A7r5 aortic smooth muscle cells. 861 Oct 34

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

The mechanism of stimulation of Ca2+ entry into hepatocytes by adenosine was investigated. When Fura-2-loaded hepatocytes were suspended in a nominally Ca(2+)-free buffer, adenosine produced only a small transient increase in the cytosolic free Ca2+ concentration ([Ca2+)i). However, on restoration of an extracellular Ca2+ concentration of 1.3 mM, a rapid increase in [Ca2+]i occurred, which indicates activation of a Ca(2+)-influx pathway. Adenosine augmented the rate of Ca2+ influx triggered by maximally effective concentrations of thapsigargin or cAMP, but was without effect on the rate of Ca2+ entry that resulted from phospholipase-C-linked-receptor activation by maximally effective concentrations of vasopressin or ATP. However, in contrast to vasopression and ATP, adenosine did not stimulate Mn2+ entry. The rate of Mn2+ influx after stimulation of the hepatocytes with vasopressin was not increased by adenosine treatment. The stimulation of hepatocytes with adenosine did not result in significant accumulation of inositol phosphates or cAMP. Furthermore, the rate of adenosine-induced Ca2+ entry in hepatocytes was only slightly reduced in the presence of the P1 purinoceptor antagonist 8-phenyltheophylline. In contrast, the receptor-mediated-Ca(2+)-entry antagonist SK&F 96365 nearly completely blocked the Ca(2+)-entry response without any effect on internal-Ca(2+)-pool mobilisation by adenosine. It is concluded that adenosine activates the internal-pool-regulated pathway of Ca2+ entry and an additional pathway that appears comparable to the previously reported receptor-dependent pathway, except that Mn2+ entry is not stimulated.
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PMID:Adenosine stimulates calcium influx in isolated rat hepatocytes. 868 74

The role of extracellular chloride in the regulation of mesangial cell calcium responsiveness to vasopressor peptides was explored. First, the components of vasopressor-stimulated calcium signaling were defined in rat mesangial cells cultured on coverslips and preloaded with fura 2. By spectrofluorometry, manganese uptake (reflecting divalent cation channel activation) was observed by quenching of fura 2, or intracellular cytosolic calcium concentration was calculated by dual-excitation ratiometric measurement. In cells depolarized with KCl (45 mM), enhanced manganese uptake or increased cytosolic calcium were inhibited with verapamil (10 microM). Pretreatment of mesangial cells with verapamil reduced the sustained calcium level in response to endothelin-1 (0.1 microM) by 65 +/- 6% (means +/- SE, n = 12) and to vasopressin (1 microM) by 62 +/- 12% (n = 8). Perforated cell patch-clamp measurement confirmed that endothelin-1 stimulated a sustained increase in cytosolic calcium or divalent cation entry only in the presence of simultaneous depolarization. In chloride-free buffer (chloride replaced with impermeant anions), sustained calcium response to endothelin-1 was reduced by 72 +/- 8 (n = 8) and by 65 +/- 4% (n = 8) in the presence of the chloride channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic acid (55 microM). In chloride-free buffer, cytosolic calcium (unstimulated) increased to > 200 nM by 30 min. These data indicate that reduced extracellular chloride increases mesangial cell basal cytosolic calcium and decreases the transient and sustained cytosolic calcium response to vasopressor peptides.
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PMID:Extracellular chloride regulates mesangial cell calcium response to vasopressor peptides. 876 Feb 39

The expression of hepatocyte plasma membrane receptor-activated divalent cation channels in immature (stages V and VI) Xenopus laevis oocytes and the properties which allow these channels to be distinguished from endogenous receptor-activated divalent cation channels were investigated. Divalent cation inflow to oocytes housed in a multiwell plate was measured using the fluorescent dyes Fluo-3 and Fura-2. In control oocytes, ionomycin, cholera toxin, thapsigargin, 3-fluoro-inositol 1,4,5-trisphosphate (InsP3F) and guanosine 5'-[gamma-thio]triphosphate (GTP gamma S) stimulated Ca2+ and Mn2+ inflow following addition of these ions to the oocytes. Ionomycin-, cholera-toxin-, thapsigargin- and InsP3F-stimulated Ca2+ inflow was inhibited by Gd3+ (half maximal inhibition at less thari 5 microM Gd3+ for InsP3F-stimulated Ca2+ inflow). GTP gamma S-stimulated Ca2+ inflow was insensitive to 50 microM Gd3+ and to SK&F 96365. These results indicate that at least three types of endogenous receptor-activated Ca2+ channels can be detected in Xenopus oocytes using Ca(2+)-sensitive fluorescent dyes: lanthanide-sensitive divalent cation channels activated by intracellular Ca2+ store depletion, lanthanide-sensitive divalent cation channels activated by cholera toxin, and lanthanide-insensitive divalent cation channels activated by an unknown trimeric G-protein. Oocytes microinjected with rat hepatocyte poly(A)+ RNA exhibited greater rates of Ca2+ and Mn2+ inflow in the basal (no agonist) state, greater rates of Ca2+ inflow in the presence of vasopressin or InsP3F and greater rates of Ba2+ inflow in the presence of InsP3F, when compared with "mock"-injected oocytes. In poly(A)+ RNA-injected oocytes, vasopressin- and InsP3F-stimulated Ca2+ inflow, but not basal Ca2+ inflow, was inhibited by Gd3+. It is concluded that at least one type of hepatocyte plasma membrane divalent cation channel, which admits Mn2+ as well as Ca2+ and is lanthanide-insensitive, can be expressed and detected in Xenopus oocytes.
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PMID:Injection of rat hepatocyte poly(A)+ RNA to Xenopus laevis oocytes leads to expression of a constitutively-active divalent cation channel distinguishable from endogenous receptor-activated channels. 879 84

Inositol-phosphoglycan (IPG) is a putative mediator of insulin action that has been shown to affect numerous biochemical processes. IPG, prepared from liver membranes, promptly inhibited phenylephrine- or vasopressin-induced [Ca2+]i oscillations when perfused over Fura-2-dextran injected rat hepatocytes. An antibody to IPG suppressed the inhibitory effect of insulin on the [Ca2+]i oscillations. Measurement of the rate of quench of cytoplasmic Fura-2 by extracellular Mn2+ showed that Ca2+ entry occurred continuously in the unstimulated cell and was not affected by phenylephrine or vasopressin. IPG, specifically, almost completely abolished the Mn2+ quench rate. Elevated extracellular [Ca2+] reversed the inhibitory effect of IPG on [Ca2+]i oscillations. We conclude that IPG inhibits the hepatocyte Ca2+ oscillatory by reducing the continuous Ca2+ influx that is required to sustain oscillations in [Ca2+]i.
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PMID:Inositol-phosphoglycan inhibits calcium oscillations in hepatocytes by reducing calcium entry. 913 95

1. The effect of externally applied ATP on cytosolic free Ca2+ concentration ([Ca2+]i) was tested in single isolated rat neurohypophysial nerve terminals by fura-2 imaging. The release of vasopressin (AVP) and oxytocin (OT) upon ATP stimulation was also studied from a population of terminals using specific radioimmunoassays. 2. ATP evoked a sustained [Ca2+]i increase, which was dose dependent in the 1-100 microM range (EC50 = 4.8 microM). This effect was observed in only approximately 40 % of the terminals. 3. Interestingly, ATP, in the same range (EC50 = 8.6 microM), evoked AVP, but no significant OT, release from these terminals. 4. Both the [Ca2+]i increase and AVP release induced by ATP were highly and reversibly inhibited by suramin, suggesting the involvement of a P2 purinergic receptor in the ATP-induced responses. Pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), another P2 purinergic receptor antagonist, strongly reduced the ATP-induced [Ca2+]i response. 5. To further characterize the receptor, different agonists were tested, with the following efficacy: ATP = 2-methylthio-ATP > ATP-gamma-S > alpha, beta-methylene-ATP > ADP. The compounds adenosine, AMP, beta, gamma-methylene-ATP and UTP were ineffective. 6. The ATP-dependent [Ca2+]i increase was dependent on extracellular Ca2+ concentration ([Ca2+]o). Fluorescence-quenching experiments with Mn2+ showed that externally applied ATP triggered a Mn2+ influx. The ATP-induced [Ca2+]i increase and AVP release were independent of and additive to a K+-induced response, in addition to being insensitive to Cd2+. The ATP-induced [Ca2+]i increase was strongly reduced in the presence of Gd3+. These results suggest that the observed [Ca2+]i increases were elicited by Ca2+ entry through a P2X channel receptor rather than via a voltage-dependent Ca2+ channel. 7. We propose that ATP, co-released with neuropeptides, could act as a paracrine-autocrine messenger, stimulating, via Ca2+ entry through a P2X2 receptor, the secretion of AVP, in particular, from neurohypophysial nerve terminals.
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PMID:ATP-evoked increases in [Ca2+]i and peptide release from rat isolated neurohypophysial terminals via a P2X2 purinoceptor. 967 66


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