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)

Calcium uptake in cells occurs through specific membrane channels. Since cadmium and mercury inhibit calcium uptake, this study examined whether the calcium channels may also be involved in the uptake of these metals. Primary cultures of rat hepatocytes were incubated with 3 microM CdCl2 or HgCl2 in the absence or presence of four different organic calcium channel blockers or a calcium agonist. The calcium channel blockers had no significant effect on mercury accumulation. In comparison, the uptake of cadmium was inhibited by diltiazem and verapmil (50-250 microM) as well as by nifedipine and nitrendipine (25-100 microM), with a maximum inhibition of 31% after 30 min incubation with 250 microM verapamil. The calcium agonist vasopressin (20 nM) increased cadmium accumulation by 15%. This effect was blocked by 250 microM verapamil. Kinetic analysis showed that verapamil decreased the Vmax of cadmium uptake, without altering the Km, indicating a noncompetitive inhibition. The calcium channel blockers were ineffective at 4 degrees C. These data suggest that about a third of the cadmium enters hepatocytes through the calcium channels. The mechanism of mercury uptake, on the other hand, is very different as it does not appear to involve the calcium channels.
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PMID:Differences in cadmium and mercury uptakes by hepatocytes: role of calcium channels. 165

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

We studied the effects of activation of the metabotropic glutamate receptors on intrinsic currents of magnocellular n urons of the supraoptic nucleus (SON) with whole cell patch-clamp and conventional intracellular recordings in coronal slices (400 micron) of the rat hypothalamus. Trans-(+/-)-1-amino-1,3-cyclopentane dicarboxylic acid (trans-ACPD, 10-100 microM), a broad-spectrum metabotropic glutamate receptor agonist, evoked an inward current (18.7 +/- 3.45 pA) or a slow depolarization (7.35 +/- 4.73 mV) and a 10-30% decrease in whole cell conductance in approximately 50% of the magnocellular neurons recorded at resting membrane potential. The decrease in conductance and the inward current were caused largely by the attenuation of a resting potassium conductance because they were reduced by the replacement of intracellular potassium with an equimolar concentration of cesium or by the addition of potassium channel blockers to the extracellular medium. In some cells, trans-ACPD still elicited a small inward current after blockade of potassium currents, which was abolished by the calcium channel blocker, CdCl2. Trans-ACPD also reduced voltage-gated and Ca2+-activated K+ currents in these cells. Trans-ACPD reduced the transient outward current (IA) by 20-70% and/or the IA-mediated delay to spike generation in approximately 60% of magnocellular neurons tested. The cells that showed a reduction of IA generally also showed a 20-60% reduction in a voltage-gated, sustained outward current. Finally, trans-ACPD attenuated the Ca2+-dependent outward current responsible for the afterhyperpolarization (IAHP) in approximately 60% of cells tested. This often revealed an underlying inward current thought to be responsible for the depolarizing afterpotential seen in some magnocellular neurons. (RS)-3,5-dihydroxyphenylglycine, a group I receptor-selective agonist, mimicked the effects of trans-ACPD on the resting and voltage-gated K+ currents. (RS)-alpha-methyl-4-carboxyphenylglycine, a group I/II metabotropic glutamate receptor antagonist, blocked these effects. A group II receptor agonist, 2S,1'S,2'S-2carboxycyclopropylglycine and a group III receptor agonist, (+)-2-amino-4-phosphonobutyric acid, had no effect on the resting or voltage-gated K+ currents, indicating that the reduction of K+ currents was mediated by group I receptors. About 80% of the SON cells that were labeled immunohistochemically for vasopressin responded to metabotropic glutamate receptor activation, whereas only 33% of labeled oxytocin cells responded, suggesting that metabotropic receptors are expressed preferentially in vasopressinergic neurons. These data indicate that activation of the group I metabotropic glutamate receptors leads to an increase in the postsynaptic excitability of magnocellular neurons by blocking resting K+ currents as well as by reducing voltage-gated and Ca2+-activated K+ currents.
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PMID:Modulation of multiple potassium currents by metabotropic glutamate receptors in neurons of the hypothalamic supraoptic nucleus. 940 56

The effects of ethanol were studied on single evoked spikes recorded at 20 degrees C with the perforated-patch method in acutely dissociated rat supraoptic neurons. In seven out of eight neurons, ethanol (50 mM) significantly reduced the spike duration by selectively decreasing the decay time (82+/-2% of the control), leaving the amplitude and rise time unaffected. Resting potential and threshold did not change. Similarly, CdCl2 at a concentration of 100 microM, which blocks all voltage-activated calcium current in the supraoptic neurons, reduced the decay time of single evoked spikes (76+/-3% of the control, n=10) without modifying the other above-mentioned parameters. In addition, exposure to 100 microM CdCl2 prevented any subsequent effect of 50 mM ethanol (n = 5). Exposure to apamin (10 nM) and iberiotoxin (10 nM) did not have any effect on single evoked spikes. Because these concentrations are effective in blocking, respectively, small (SK) and large (BK) conductance calcium-dependent potassium channels in these neurons, this result shows that these currents are not involved in either the shaping of single evoked spikes or the actions of ethanol on spike shape. The sustained component of whole-cell recorded calcium current measured at -10 mV (hp -60 mV) was inhibited by ethanol in a dose-dependent manner, with a significant effect detectable at 25 mM. Exposure to 50 mM ethanol significantly reduced the sustained current to 70+/-5% of the control (n=12), without any apparent shift of the current-voltage relationship. Control exposure of the neurons to either 50 mM urea or 50 mM sucrose did not affect the voltage-gated calcium currents. We conclude that ethanol reduces the duration of single evoked spikes by a specific inhibition of voltage-activated calcium currents. The results suggest that, in addition to its direct effects on release of vasopressin and oxytocin from neurohypophysial terminals, ethanol could also affect hormonal release via changes in firing patterns arising in the cell bodies.
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PMID:Ethanol reduces the duration of single evoked spikes by a selective inhibition of voltage-gated calcium currents in acutely dissociated supraoptic neurons of the rat. 968 42

Populations of hepatocytes in primary culture were loaded with fura 2 and the effects of extracellular heavy-metal ions were examined under conditions that allowed changes in fura 2 fluorescence (R340/360, the ratio of fluorescence recorded at 340 and 360 nm) to be directly attributed to changes in cytosolic free [Ca2+] ([Ca2+]i). In Ca2+-free media, Ni2+ [EC50 (concentration causing 50% stimulation) approximately 24+/-9 microM] caused reversible increases in [Ca2+]i that resulted from mobilization of the same intracellular Ca2+ stores as were released by [Arg8]vasopressin. The effects of Ni2+ were not mimicked by increasing the extracellular [Mg2+], by addition of MnCl2, CoCl2 or CdCl2 or by decreasing the extracellular pH from 7.3 to 6.0; nor were they observed in cultures of smooth muscle, endothelial cells or pituitary cells. CuCl2 (80 microM), ZnCl2 (80 microM) and LaCl3 (5 mM) mimicked the ability of Ni2+ to evoke Ca2+ mobilization. The response to La3+ was sustained even in the absence of extracellular Ca2+, probably because La3+ also inhibited Ca2+ extrusion. Although Ni2+ entered hepatocytes, from the extent to which it quenched fura 2 fluorescence the free cytosolic [Ni2+] ([Ni2+]i) was estimated to be <5 nM at the peak of the maximal Ni2+-evoked Ca2+ signals and there was no correlation between [Ni2+]i and the amplitude of the evoked increases in [Ca2+]i. We conclude that extracellular Ni2+, Zn2+, Cu2+ and La3+, but not all heavy-metal ions, evoke an increase in [Ca2+]i in hepatocytes by stimulating release of the hormone-sensitive intracellular Ca2+ stores and that they may do so by interacting with a specific cell-surface ion receptor. This putative ion receptor may be important in allowing hepatocytes to contribute to regulation of plasma heavy-metal ions and may mediate responses to Zn2+ released into the portal circulation with insulin.
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PMID:Extracellular heavy-metal ions stimulate Ca2+ mobilization in hepatocytes. 1021 93