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)

Isolated neural lobes of the rat pituitary gland were fixed by their stalks to a platinum wire electrode. They were loaded with 45calcium and then superfused with radioactivity-free Krebs-solution. The efflux of 45calcium into the superfusion medium was determined. After 54-60 min of superfusion the spontaneous outflow of 45calcium was 2.03%/min of the tissue 45calcium. It was not affected by cadmium (Cd2+, 0.03-3 mmol/l), but reduced by 40% in the presence of 1 mmol/l gadolinium (Gd3+). Electrical stimulation with pulses of 15 Hz (3 times for 1 min with intervals of 1 min) evoked a 45calcium release of 14.4% of the tissue radioactivity. The evoked release of 45calcium was reduced by 80% in the presence of tetrodotoxin and by about 50% in the presence of gallopamil (D600, 30 mumol/l) or after omission of unlabelled calcium from the superfusion medium. Gd3+ concentration-dependently reduced the evoked release by maximally 75% at 3 mmol/l. However, it inhibited the evoked release of 45calcium less effectively than the release of vasopressin evoked by identical stimulation conditions. Cd2+ reduced the evoked release by maximally 55% at 300 mumol/l. The effect of Cd2+ on the evoked release of vasopressin was not tested because Cd2+ markedly increased the spontaneous outflow of vasopressin. When the stimulation was carried out for only 1 min at 15 Hz (i.e. 900 pulses) the evoked release of 45calcium was 10.6% of the tissue 45calcium and 100 mumol/l Cd2+ or 300 mumol/l Gd3+ caused a reduction of the evoked release similar to that observed when 3 periods of stimulation were applied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of gadolinium and cadmium on the electrically evoked release of 45calcium from the isolated rat neurohypophysis. 339 32

1. Single neurohypophyses from male rats were maintained in an in vitro perifusion chamber. Ion-sensitive microelectrodes were introduced into the tissue to measure changes in [K+]o and [Ca2+]o during electrical stimulation. 2. Electrical stimulation at 6 Hz for 1 min and 30 Hz for 12 s raised [K+]o by 5.4 +/- 0.4 and 13.5 +/- 0.5 mM (mean +/- S.E.M., n = 8) respectively. To investigate the effects of raised [K+]o on the excitability of the neurosecretory terminals, stimulations were repeated in media of altered K+ concentration. The increase in [K+]o evoked by 6 Hz stimulation was elevated in 10 mM-K+ medium (133% of that in 5 mM-K+ medium) and reduced in 0 mM-K+ medium and in 25 mM-K+ medium. Thus it appeared that stimulus-induced changes in [K+]o might enhance the excitability of the tissue during electrical activation. 3. To test this hypothesis, we measured the field potential responses evoked by 0.5 Hz stimulation in media of different K+ concentrations. The size of the field potential was enhanced in 10 mM-K+ medium and depressed in 0 mM-K+ medium and in 25 mM-K+ medium. 4. Electrical stimulation (6 Hz, 1 min) decreased [Ca2+]o by 10.9 +/- 1.8% (n = 6). This decrease was absent in the presence of 1 microM-tetrodotoxin or 1 mM-cadmium. Again, the [Ca2+] response to stimulation was enhanced in 10 mM-K+ medium and depressed in 0 mM-K+ medium or 25 mM-K+ medium. 5. The release of vasopressin and oxytocin evoked by stimulation at 6 or 30 Hz from isolated neurohypophyses was measured by radioimmunoassay in a separate series of experiments. Stimulation at 30 Hz for 1 min released 5- to 6-fold more hormone than stimulation at 6 Hz for 5 min. Release evoked by 6 Hz stimulation was enhanced in 15 mM-K+ medium and depressed in 25 mM-K+ medium. 6. We conclude that the rise in [K+]o that accompanies high-frequency activation of axons and terminals in the neurohypophysis contributes to the facilitation of hormone release with increasing frequencies of stimulation, and in particular to the efficiency of the milk-ejection burst discharge of oxytocin neurones for evoking oxytocin release.
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PMID:Effects of raised extracellular potassium on the excitability of, and hormone release from, the isolated rat neurohypophysis. 340 69

Peritoneal cells from thioglycollate-stimulated mice were allowed to adhere to coverglasses for 2 h to give a dense monolayer of adherent cells greater than 95% of which were macrophages. After incubation with the tetra-acetoxymethyl ester of quin2, coverglasses were rinsed with Ca2+-free saline, oriented at a 45 degree angle in square cuvettes containing a magnetically driven stir bar, and analyzed for changes in quin2 fluorescence in a spectrofluorimeter. Such fluorescence, taken as an indication of intracellular calcium ion concentration ([Ca2+]i), increased as exogenous calcium ion concentration ([Ca2+]o) was raised to 1 mM. At [Ca2+]o approximately equal to 10 microM, [Ca2+]i = 72 +/- 14 nM (n = 26); at [Ca2+]o = 1 mM, [Ca2+]i = 140-220 nM, levels not increased by N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine, a membrane-permeant chelator of heavy metals than can quench quin2. Addition of mouse alpha + beta fibroblast interferon, lipopolysaccharide, thrombin, collagen, vasopressin, ADP, compound 48/80, or U46619 did not change [Ca2+]i. However, addition of platelet activating factor (PAF) (2-20 ng/ml) raised [Ca2+]i by 480 nM within 1 min if [Ca2+]o = 1 mM. In the presence of 5 mM EGTA, PAF raised [Ca2+]i by 25 nM. This suggests that PAF causes influx of exogenous Ca2+, as well as releasing some Ca2+ from intracellular stores. Consistent with these results, when PAF was added to 1 mM Ca2+ in the presence of 100 microM Cd2+ or Mn2+ to block Ca2+ influx, [Ca2+]i increased by only intermediate amounts; at the times of such dampened peak response, [Ca2+]i could be raised within 1 min to normal PAF-stimulated levels by chelation of the exogenous heavy metals with diethylenetriaminepentaacetic acid. Normal PAF responses were observed in the presence of indomethacin. The lowest dose of PAF observed to raise [Ca2+]i was 0.1 ng/ml. Response of [Ca2+]i to 2-20 ng/ml PAF was transient, and second applications had no effect. The PAF response also was seen in cell suspensions. These results suggest that an increase in [Ca2+]i may be an early event in PAF activation of macrophages.
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PMID:Platelet activating factor raises intracellular calcium ion concentration in macrophages. 373 74

The effect of (R,S)-(3,4-dihydro 6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl- N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908), a cation channel blocker in HL-60 promyeloblasts, was studied in the A7r5 smooth muscle cell line from rat thoracic aorta, using the whole-cell patch-clamp technique. At a holding potential of -60 mV, application of vasopressin induced a nonselective cation conductance in voltage-clamped A7r5 cells. The current-voltage relation was linear, and currents reversed close to 0 mV regardless of the chloride gradient. The activation of the nonselective cation conductance by vasopressin was not affected by dialysing cells with Ca(2+)-free internal solution. LOE 908 blocked this current in a concentration-dependent manner with an IC50 of 560 nM, whereas dihydropyridine-sensitive Ba2+ current through voltage-dependent Ca2+ channels was blocked with an IC50 of 28 microM. Another organic blocker of receptor-mediated Ca2+ entry, 1-beta-[3-(4-methoxyphenyl)-propoxy]-4-methoxyphenethyl-1H-imidazole hydrochloride (SK&F 96365), blocked both, the vasopressin-induced nonselective conductance and the voltage-activated Ba2+ current with similar IC50 values of 13 microM and 8 microM, respectively. The rank order of potency of inorganic blockers on the vasopressin-induced inward current was Gd3+ > La3+ > Cd2+. Vasopressin-induced non-selective cation current was also observed in pertussis toxin-pretreated A7r5 cells but was completely abolished after infusion of the GDP analogue, guanosine 5'-O-[3-thio]diphosphate, from the patch pipette. Furthermore, vasopressin induced a transient outward current, suggesting a Ca(2+)-activated K(+)-current, which overlapped with the nonselective cation conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The isoquinoline derivative LOE 908 selectively blocks vasopressin-activated nonselective cation currents in A7r5 aortic smooth muscle cells. 751 40

The noncontractile aortic cell line A7r5 was chosen to study the effect of the vasoconstrictor peptide vasopressin on transmembrane Ca2+ movements, using conventional whole-cell patch recording techniques. Conditions in which previously characterised vasoconstrictor-modulated currents were suppressed revealed a tiny inward current component (-18 +/- 2 pA, n = 50, at -61 mV in 110 mM CaCl2). The vasopressin-activated inward current was absent when Ca2+ was absent from the extracellular solution, and the current amplitude increased with [Ca2+] (0.01-110 mM), with an apparent dissociation constant for Ca2+ of 9.7 mM. It was highly selective for Ca2+ over monovalent cations (permeability ratio Ca/Cs greater than 17). It was not voltage gated, except that the current/potential characteristic showed some inwards rectification. Amplitudes of the evoked inward currents had the same order of magnitude in Sr2+ and Ca2+, whereas they were much smaller in Mn2+, suggesting that this pathway is highly permeable to Sr2+ but poorly permeable to Mn2+. Inward currents evoked in Ca2+ were inhibited by other cations with the following order of potency: La3+ > Cd2+ > Co2+ approximately Ni2+ approximately Mn2+. The channel producing this current corresponds most probably to the ionic pathway originally called the receptor-operated calcium channel, which produces a long-lasting, constrictor-induced plateau of increased intracellular free calcium concentration in smooth muscle.
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PMID:Identification of the Ca2+ current activated by vasoconstrictors in vascular smooth muscle cells. 770 69

We examined the effect of the depletion of intracellular Ca2+ stores on Ca2+ influx in rat glomerulosa cells. Depletion of intracellular Ca2+ stores was achieved by inhibiting sarco/endoplasmic reticulumtype Ca(2+)-ATPase with thapsigargin or 2,5,di-(t-butyl)-1,4-benzohydroquinone (t-BHQ). Both inhibitors induced a sustained rise in cytoplasmic Ca2+ concentration. The initial rise was observed also in Ca(2+)-free medium, while the sustained phase disappeared, indicating that the latter requires Ca2+ influx. In Ca(2+)-free medium, the readdition of Ca2+ induced a steeper and higher rise in intracellular Ca2+ concentration in thapsigargin-treated cells than in controls, supporting the role of Ca2+ influx. In normal medium, the addition of Cd2+ (80 microM) evoked an immediate inhibition of the sustained phase of thapsigargin response. The response to thapsigargin was insensitive to nifedipine. Thapsigargin failed to enhance Mn2+ quenching of fura 2. Our results provide evidence for the existence of capacitative Ca2+ influx in rat glomerulosa cells and indicate that dihydropyridine-sensitive Ca2+ channels do not participate in capacitative Ca2+ entry. High concentrations of thapsigargin and t-BHQ, similar to the reported effects of angiotensin II and vasopressin, inhibited K(+)-induced Ca2+ signals. These effects appear, however, to be independent of the depletion of internal Ca2+ stores.
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PMID:Capacitative Ca2+ influx in adrenal glomerulosa cells: possible role in angiotensin II response. 797 88

Cadmium, a trace element from natural and industrial sources, may contribute to the pathogenesis of arterial hypertension. We evaluated the effect induced by acute intracerebroventricular (icv) administration of cadmium on mean blood pressure of normotensive conscious rats. Intracerebroventricular cadmium (1 to 10 micrograms) produced a dose-dependent, sustained increase in mean blood pressure. The hypertensive response to icv cadmium was significantly (P < .01) prevented by icv pretreatment with verapamil (10 to 100 micrograms). A preventive effect was exerted also by icv nifedipine (100 micrograms); however, this result was attributable, at least in part, to the antihypertensive action of the vehicle, polyethylene glycol. The hypertensive response to icv cadmium was blunted by icv administration of 10 ng clonidine, 10 micrograms vasopressin antagonist, or 10 micrograms bradykinin antagonist (P < .05), but it was not altered by icv enalaprilat (100 micrograms). These results indicate that brain calcium channels play a role in the hypertensive action induced by icv cadmium. Accumulation of cadmium in the brain caused by prolonged exposure to this heavy metal might lead to chronic arterial hypertension.
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PMID:Verapamil prevents the acute hypertensive response to intracerebroventricular cadmium in conscious normotensive rats. 846 5

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 effects of vasopressin and endothelin-1 on cultured aortic smooth muscle cell lines (A7r5) were investigated by measurements of intracellular calcium [Ca2+]i and the patch-clamp techniques. Vasopressin and endothelin-1 (100 nM) evoked an initial peak followed by a smaller sustained rise of [Ca2+]i in the presence of extracellular calcium [Ca2+]o. In the absence of [Ca2+]o, only the initial peak of [Ca2+]i was observed. Therefore, the initial peak of [Ca2+]i was mainly due to calcium release from the storage sites, whereas the later sustained rise of [Ca2+]i was due to the calcium entry from outside. The sustained rise of [Ca2+]i was unaffected by nifedipine (10 microM) significantly, but was completely abolished by La3+ (1 mM). Under current clamp conditions with K(+)-internal solution, vasopressin and endothelin-1 (100 nM) produced hyperpolarization, then followed by depolarization. Under voltage clamp conditions at a holding potential of -40 mV, both vasopressin and endothelin-1 first activated the outward current, then followed by a long-lasting inward current with a high noise level. The first outward current was abolished by charybdotoxin (100 nM), Cs+ in the patch pipette and high EGTA (10 mM) in the pipette, suggesting that it was a Ca(2+)-sensitive K+ current (IK.Ca). The inward current was still elicited with the patch pipette containing Cs(+)-internal solution, and reversed at about 0 mV. The reversal potential was not significantly altered by the replacement of [Cl-]i or [Cl-]o, proposing that the inward current is a cation selective channel (IN.S.). The inward current was also observed even when extracellular cations are Ca2+. La3+ (1 mM), Cd2+ (1 mM) completely abolished the vasopressin-induced (IN.S.), however, nifedipine (10 microM) failed to inhibit it significantly. Single channel activities were recorded in the cell-attached configurations when vasopressin or endothelin-1 was applied to the bathing solution. The unitary conductance of the channels was approximately 20 pS with 140 mM Na+, Cs+, or K+ in the pipette, but was 15 pS with 110 mM Ca2+ in the pipette. Permeabilities sequence calculated from the reversal potentials was Na+ not equal to Cs+ not equal to K+ > Ca+. These results provide evidence that calcium entry and membrane depolarization elicited by vasopressin or endothelin-1 are mediated by a receptor-mediated Ca(2+)-permeable non-selective cation channel in aortic smooth muscle cells.
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PMID:Endothelin-1 and vasopressin activate Ca(2+)-permeable non-selective cation channels in aortic smooth muscle cells: mechanism of receptor-mediated Ca2+ influx. 873 99

To elucidate the mechanisms of estrogens-induced relaxation effects on vascular smooth muscle cells, the effects of estrogens and the related hormones were examined in cultured rat thoracic aortic smooth muscle cell lines (A7r5), using the whole-cell voltage clamp technique. The patch pipette was filled with 140 mM CsCl- or KCl-containing internal solution. With CsCl-internal solution, 17beta-estradiol and synthetic estrogens, ethynylestradiol and diethylstilbestrol (0.1-30 mu M) inhibited the Ba2+ inward current (IBa) through the voltage-dependent L-type Ca2+ channel in a concentration-dependent and reversible manner. The potency of the inhibitory effects on IBa was 17beta-estradiol < ethynylestradiol < diethylstilbestrol. 17beta-Estradiol (10 mu M) appeared to reduce the maximal conductance of IBa with only a slight shift of voltage-dependency of inactivation and to affect IBa in a use-independent fashion. On the other hand, testosterone and progesterone (30 mu M) failed to affect IBa. At a holding potential of -40 mV, both vasopressin and endothelin-1 (100 nM) activated a long-lasting inward current. After endothelin-1 (100 nM) activated the current, the additional application of vasopressin (100 nM) could not induce it furthermore, suggesting that each agonist activates the same population of the channels. The reversal potential of the current was about 0 mV and was not significantly altered by replacement of [Cl-]i or [Cl-]0 and the inward current was also observed even when extracellular cations are Ca2+, proposing that it was a Ca2+-permeable non-selective cation channel (IN.S.). La3+ or Cd2+ (1 nM) completely abolished IN.S., however, nifedipine (10 mu M) failed to inhibit it at all. Diethylstilbestrol (1-30 mu M) suppressed the IN.S. evoked by both endothelin-1 and vasopressin in a concentration-dependent manner, while 17beta-estradiol, ethynylestradiol, progesterone and testosterone (30 mu M) failed to inhibit it significantly. In addition, at a holding potential of +0 mV, 17beta-estradiol by itself did not affect the holding currents, and did not inhibit K+ currents evoked by endothelin-1 or vasopressin, possibly due to the Ca2+ release from the storage sites. These results suggest that 17beta-estradiol may play a role in regulating vascular tone, selectively by inhibiting the voltage-dependent L-type Ca2+ current in vascular smooth muscle cells.
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PMID:17beta-Estradiol inhibits the voltage-dependent L-type Ca2+ currents in aortic smooth muscle cells. 875 Jul 27


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