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J Llopis

Publications and source records attributed to J Llopis.

At least 55 records · Page 3Linked to original sources
PubMed1994

Changes in bioavailability and tissue distribution of zinc caused by magnesium deficiency in rats.

The effect of a Mg-deficient diet (200 mg Mg/kg feed) on the bioavailability of dietary Zn and the concentration of this cation in plasma, whole blood, skeletal muscle, kidney, heart and brain of Wistar rats was studied after 7, 35, 42, 49, 56, 63 and 70 d. Mg deficiency significantly decreased Zn in whole blood on day 42 of the experiment, but there was no significant change in plasma Zn throughout the 70 d study period. The Mg-deficient diet significantly increased intestinal absorption of Zn, Zn balance, and Zn concentration in femur and kidney, but decreased Zn concentration in the heart despite the increase in dry weight of this organ. No change was found in brain Zn concentration.

Animals↗
PubMed1993

Eicosanoids released following inhibition of the endoplasmic reticulum Ca2+ pump stimulate Ca2+ efflux in the perfused rat liver.

In the isolated perfused rat liver 2,5-di(tert-butyl)hydroquinone (tBuHQ), a selective inhibitor of the endoplasmic reticulum Ca2+ pump, induces a prolonged glucose output and stimulates Ca2+ efflux. The present study shows that tBuHQ depleted the hormone-sensitive Ca2+ pool in the perfused liver, abolishing the vasopressin- or phenylephrine-induced Ca2+ efflux. The effects of tBuHQ were reversible, since the response to these agonists gradually returned within 1 hr of perfusion, and protein synthesis was not required for this recovery. Since tBuHQ does not cause Ca2+ efflux from isolated hepatocytes, we examined the mechanism responsible for the tBuHQ-induced Ca2+ efflux observed in the intact liver. The cyclooxygenase inhibitor indomethacin prevented the Ca2+ extrusion stimulated by tBuHQ, but not that induced by vasopressin. During infusion of tBuHQ there was a 9-fold increase in the concentration of thromboxane B2 in the perfusate. The Ca2+ efflux response to tBuHQ was inhibited by the thromboxane/prostaglandin endoperoxide receptor antagonist, L-655,240 (3-[1-(4-chlorobenzyl)-5-fluoro-3-methyl-indol-2-yl]2,2-dimethylpropa noic acid) in the absence of any effect on thromboxane B2 release. Thus, the inhibition of the endoplasmic reticulum Ca2+ pump by tBuHQ results in a rise in the cytosolic Ca2+ concentration in non-parenchymal cells, leading to the formation of cyclooxygenase products. The released eicosanoids, in turn, stimulate Ca2+ efflux from hepatocytes.

Animals↗
PubMed1993

Effects of a magnesium-deficient diet on sleep organization in rats.

The influence of magnesium, one of the most important cations in the vertebrate body, on the sleep-wakefulness cycle and ECoG patterns in chronically implanted rats recorded during the light period over a 6-hour period was investigated. Two groups of rats were studied. Group 1 (6 rats): after a control period of 2 weeks, the rats were maintained for 9 weeks on a Mg(2+)-deficient diet. Group 2 (5 rats): after a control period of 2 weeks, the rats were maintained for 7 weeks on a Mg(2+)-deficient diet followed by 4 weeks on a normal diet (recovery period: weeks 8-11). Mg(2+)-deficient diet for 9 weeks induced sleep and ECoG time-dependent alterations. After 6-7 weeks on a Mg(2+)-deficient diet (n = 11) sleep analysis showed a significant increase of wakefulness (+50%) at the expense of slow wave sleep (-24%) but paradoxical sleep was not significantly modified. After 9 weeks of a Mg2+ deficient diet, sleep was disorganized: light sleep and polyspikes occurred indicating an increase in neuronal excitability. When Mg2+ was reintroduced in food and water, sleep organization and ECoG recordings were restored to their original patterns. Our findings which are in line with previous clinical and pharmacological observations provide conclusive arguments for the neuroprotective effect of magnesium ions in neurologic disorders and epileptiform activity. Mg2+ deficiency induces ECoG alterations in the rat which bear some similarities with those seen in neurogenic spasmophilic syndromes in man.

Animals↗
PubMed1993

Evolution of Mg deficiency in rats.

We performed weekly analyses of the evolution of the bioavailability of the Mg cation over a period of 70 days in adult rats fed an Mg-deficient (0.02%) diet. The results generally showed an increase in digestive utilization (% absorption) and a decrease in Mg balance during the experimental period. The parameters most sensitive to Mg deficiency were increase in body weight and blood concentration of Mg (mg/100 ml), which had declined significantly after 7 days (p < 0.05). Significant declines in plasma (p < 0.02) and muscle Mg (p < 0.01) were not apparent until after 35 days. Magnesium content in bone decreased from day 49 onward (p < 0.05), whereas renal Mg concentration tended to rise slightly during the last 2 weeks of study. No change was found in brain Mg concentration.

Absorption↗
PubMed1992

H7, a protein kinase C inhibitor, increases the glutathione content of neuroblastoma cells.

It is shown that the intracellular glutathione (GSH) concentration of neuroblastoma-2a cells in culture increases with a maximum at 24 h after starting treatment with 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), an inhibitor of protein kinase C (PKC). Other inhibitors of this and other protein kinases, e.g. sphingosine, staurosporine, and HA 1004, at the concentrations tested, had a less marked or negligible effect on intracellular GSH concentration. 12-O-Tetradecanoylphorbol-13-acetate (TPA) was also tested and showed no significant effect 24 h after addition.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Evidence for two pathways of receptor-mediated Ca2+ entry in hepatocytes.

Receptor-mediated Ca2+ entry was studied in fura-2-loaded isolated hepatocytes. Emptying of internal Ca2+ stores by treatment with either the Ca(2+)-mobilizing hormone vasopressin or the inhibitors of the microsomal Ca2+ pump, 2,5-di-(t-butyl)-1,4-benzohydroquinone (tBuBHQ) or thapsigargin, stimulated Ca2+ entry, as indicated by a rise in the cytosolic free Ca2+ concentration after Ca2+ was added to cells suspended in nominally Ca(2+)-free medium. The enhancement of Ca2+ entry was proportional to the degree of depletion of the intracellular Ca2+ pool and occurred also after removal of vasopressin from its receptor. In contrast, the stimulation of Mn2+ entry by vasopressin required the continuous presence of the agonist, since it was prevented by the addition of vasopressin receptor antagonist. This effect was observed under conditions where refilling of the agonist-sensitive pool was prevented by using nominally Ca(2+)-free medium. Unlike vasopressin, tBuBHQ or thapsigargin did not stimulate Mn2+ entry. These results suggest the existence of two pathways for receptor-mediated Ca2+ entry in hepatocytes, a 'capacitative' pathway that is sensitive to the Ca2+ content in the Ins(1,4,5)P3-sensitive Ca2+ pool and does not allow Mn2+ entry, and a second pathway that depends on receptor occupation, seems to require a second messenger for activation, and permits influx of Mn2+.

Animals↗
PubMed1992

Cytosolic Ca2+ spikes evoked by the thiol reagent thimerosal in both intact and internally perfused single pancreatic acinar cells.

Cytosolic calcium signals evoked by the sulphydryl-group-oxidising agent, thimerosal, have been investigated in acutely isolated pancreatic acinar cells. Two techniques were employed for the assessment of the cytosolic free-calcium concentration ([Ca2+]i): measurement of calcium-dependent chloride and non-specific cation currents (whole-cell patch-clamp recording) and microfluorimetry (fura-2). Thimerosal (0.5-100 microM) evoked repetitive spikes in both chloride and cation currents as seen by patch-clamp recording, and in [Ca2+]i as seen by microfluorimetry, with a latency of 1-3 min. The response increased in magnitude over time and was not reversed on removal of thimerosal. The thimerosal-induced spikes were reversibly blocked by 2 mM dithiothreitol and by 20 mM caffeine. Inclusion of heparin (200 micrograms/ml) in the pipette solution blocked the thimerosal-induced spikes. The calcium spikes continued after the removal of extracellular calcium; however, low concentrations of thimerosal (0.5-5 microM) were unable to initiate a current response in the absence of external calcium. High concentrations of thimerosal (50-100 microM) could initiate spikes without extracellular calcium. Thimerosal, at concentrations that failed to produce an independent effect, potentiated the acetylcholine-evoked oscillations in [Ca2+]i. We conclude that thimerosal is able to mobilise calcium from an intracellular store; the blockade by heparin may indicate that thimerosal exerts an action on the inositol trisphosphate pathway. The dependence on extracellular calcium for initiation, but not for continuation of the thimerosal-induced calcium spikes suggests that thimerosal may have the additional effect of inhibiting the plasma membrane calcium ATPase.

Action Potentials↗
PubMed1992

Plasma lipid composition in an elderly population: correlation with dietary fat.

The effects of dietary fat on plasma lipid composition were studied in a population of 51 elderly subjects (19 men, 32 women) who lived in a retirement home in the province of Jaén (southern Spain). Dietary intake of fat was elevated (106 and 115 g/day in men and women respectively), and fatty acid intake consisted of 40% oleic acid, 17% linoleic acid and 0.7% linolenic acid. Cholesterol intake was 506 and 518 mg/day in men and women respectively, whereas the plasma level of cholesterol was approximately 250 mg/dl in both sexes. In men and women, HDL-cholesterol levels were 71.5 and 62.2 mg/dl, and LDL-cholesterol levels were 153.5 and 152.3 mg/dl. The most abundant circulating fatty acid was palmitic acid (25%) in both sexes, followed by oleic (23%) and linoleic acid (15-16%), whereas linolenic acid represented only 0.3% of the plasma fatty acids. To determine whether plasma levels of fatty acids served as reliable biological markers of dietary fatty acid intake, we compared the two sets of values, and found that higher intake was reflected in higher plasma levels, although a significant linear correlation (p < 0.05) was found only for linolenic acid.

Aged↗
PubMed1991

Comparison between the effects of the microsomal Ca(2+)-translocase inhibitors thapsigargin and 2,5-di-(t-butyl)-1,4-benzohydroquinone on cellular calcium fluxes.

The effects of two inhibitors of the microsomal Ca(2+)-ATPase, thapsigargin and 2,5-di-(t-butyl)-1,4-benzohydroquinone, were compared in hepatocytes and in a T-cell line (JURKAT). Both compounds mobilized the same intracellular Ca2+ pool, which contained the Ins(1,4,5)P3-sensitive store, in hepatocytes and in JURKAT cells. The mobilization of the internal Ca2+ store with either compound activated Mn2+ entry in JURKAT cells, but not in hepatocytes. This suggests different properties of the bivalent-cation entry pathway between these cell types.

Animals↗
PubMed1991

Mobilization of the hormone-sensitive calcium pool increases hepatocyte tight junctional permeability in the perfused rat liver.

Hepatocyte tight junctional permeability has been shown to be regulated by hormones that exert their effects via phospholipase C activation. However, the precise transduction pathway involved in this effect is not known. The present study has employed the selective inhibitor of microsomal Ca2+ sequestration, 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), to examine the effect of the mobilization of the endoplasmic reticular Ca2+ pool on tight junctional permeability in the perfused rat liver. Infusion of tBuBHQ followed by a bolus infusion of horseradish peroxidase (HRP) resulted in a significant increase in the first peak of biliary HRP, a measure of junctional permeability, whereas transcellular (vesicular) transport of HRP was not affected. Therefore, we conclude that the effect of hormones on tight junctional permeability is mediated, at least in part, by the mobilization of intracellular Ca2+.

Animals↗
PubMed1990

Receptor-operated calcium influx in rat hepatocytes. Identification and characterization using manganese.

Agonist-stimulated divalent cation entry was studied in fura-2-loaded hepatocytes. In the presence of extracellular Mn2+, the Ca2(+)-mobilizing hormone vasopressin produced a severalfold stimulation of the basal rate of fura-2 fluorescence quenching as a result of Mn2+ influx; this effect was blocked by the presence of Ni2+ in the incubation medium. Half-maximum and maximum stimulation of Mn2+ influx was observed with 0.1 and 0.8 nM vasopressin, respectively. Agonist-stimulated Mn2+ influx was also seen with angiotensin II, ATP, phenylephrine, and the combination of AlCl3 and NaF. The stimulation of Mn2+ influx did not occur immediately after addition of Ca2(+)-mobilizing agents, but was characterized by a latency period of 20-30 s. In contrast to vasopressin, glucagon did not stimulate Mn2+ influx into hepatocytes, but produced both a 3-fold enhancement of the rate of vasopressin-stimulated Mn2+ entry and the abolishment of the latency period. The effects of glucagon were mimicked by forskolin and dibutyryl cAMP. Pretreatment of hepatocytes with pertussis toxin or depolarization of the cells altered neither the basal rate of Mn2+ entry nor the ability of vasopressin to stimulate this rate. Emptying of the inositol 1,4,5-trisphosphate-sensitive Ca2+ store by treatment with 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) did not enhance Mn2+ entry into hepatocytes; however, exposure of the cells to tBuBHQ for 2 min markedly enhanced the ability of vasopressin, alone or in combination with glucagon, to increase the rate of Mn2+ influx. Furthermore, pretreatment with tBuBHQ for 2 min abolished the latency of vasopressin-stimulated Mn2+ influx. It is concluded that Ca2(+)-mobilizing hormones stimulate Ca2+ influx in hepatocytes, possibly through receptor-operated Ca2+ channels. The stimulation of divalent cation entry is transduced by a G protein, and the rate of influx appears to be controlled both by the intracellular level of cAMP and the empty state of an intracellular Ca2+ pool that may be inositol 1,4,5-trisphosphate-insensitive.

Angiotensin II↗
PubMed1990

Influence of hydrocortisone acetate administered to the lactating rat on protein and lactose content in milk and serum protein, glucose and insulin levels in dams and pups.

The influence of i.m. administration to the mother of hydrocortisone acetate (doses of 0.4, 0.8 or 2.0 mg/100 g body weight/day) during the first 15 days of lactation on milk protein and lactose composition and serum levels of protein, glucose and insulin in dams and pups is studied. Total serum proteins and albumin/globulin ratio in dams were unchanged by treatment. The daily injection of 0.4 or 0.8 mg/100 g body weight failed to alter serum levels of glucose or insulin in dams, whereas a dose of 2.0 mg/100 g body weight led to a rise in glucemia (from 118 +/- 3.2 to 133 +/- 5.3) which was accompanied by a sharp change in insulinemia (from 40.7 +/- 4.1 to 83.6 +/- 6.9). All three doses raised protein levels in milk. The smallest increase was recorded with 2.0 mg/100 g body weight; this dose also reduced milk lactose content. Total serum proteins in pups rose slightly but nonsignificantly, and no significant effects were noted on albumin/globulin ratio or serum glucose and insulin levels.

Animals↗
PubMed1990

Recovery study in Mg-deficient rats given an organic source of Mg.

Recovery from Mg deficiency was studied in rats given an organic source of Mg derived from yeast (Saccharomyces cerevisiae) cultured in an Mg gluconate-enriched medium, as the only source of Mg. Magnesium was given either at a rate above the RDA or as a supplement to the regular laboratory diet at the rate of 70 mg Mg/100 g food, of which 40 mg Mg was in the form of MgCO3 and the remaining 30 mg Mg was in the form of the organic product under study. The results showed a good degree of digestive and metabolic utilization of the organic compound, which led to the recovery of normal Mg levels in blood and bone by the end of the 1st week of treatment, and in muscle by the 3rd week of treatment. Muscle Mg content appears to be a good indicator of deficiency. Supplementation above the RDA failed to improve recovery rates in deficient animals.

Animals↗
PubMed1990

Influence of dietary fat on the lipid composition of perirenal adipose tissue in rats.

The influence of dietary fat on the composition of perirenal adipose tissue was studied in Wistar rats fed three experimental semisynthetic, isocaloric diets containing different qualities of fat (olive oil, butter and medium chain triglycerides + corn oil). Under these experimental conditions, the saturation index reflects the percentage of fatty acids supplied by each diet; this index was highest in animals fed the diet containing butter and lowest in the group in which olive oil was the dietary fat source. The amount of linoleic acid (the major component of the diunsaturation index) supplied by the diet is directly paralleled by levels of this fatty acid in perirenal adipose tissue, whereas the monounsaturation index in adipose tissues, considered an indicator of the dietary supply of monounsaturated fatty acids in the rat, failed to show a clearly proportional relationship between intake and perirenal adipose tissue levels.

Adipose Tissue↗
PubMed1990

Release of Ca2+ from the endoplasmic reticulum is not the mechanism for bile acid-induced cholestasis and hepatotoxicity in the intact rat liver.

The hypothesis that monohydroxy bile acids exert their cholestatic and hepatotoxic effects via a sustained elevation of cytosolic [Ca2+] was tested in the isolated perfused rat liver. Infusion of the specific inhibitor of microsomal Ca2+ sequestration, 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) (25 microM for 10 min) produced efflux of Ca2+ from the liver and a sustained (20 min) increase in cytosolic [Ca2+] as indicated by the threefold increase in hepatic glucose output. Release of the endoplasmic reticular Ca2+ pool was demonstrated by the complete abolition of vasopressin- and phenylephrine-induced Ca2+ exchange between the liver and perfusate. Despite the profound perturbation of intracellular Ca2+ homeostasis produced by tBuBHQ, there was no decrease in bile flow and no evidence of hepatocellular injury (for 60 min), as indicated by lactate dehydrogenase release. In contrast, lithocholic acid (25 microM for 10 or 30 min) or taurolithocholic acid (5 microM for 10 or 30 min) produced an 80-90% inhibition of bile flow and a progressive increase in perfusate lactate dehydrogenase activity. During and after bile acid infusion, there was no change in Ca2+ fluxes between liver and perfusate, no stimulation of glucose output from the liver, and hormone-stimulated Ca2+ responses were preserved. It is concluded that the mechanisms for bile acid-induced cholestasis and hepatotoxicity in the intact liver are not attributable to changes in intracellular Ca2+ homeostasis, and especially not to prolonged release or depletion of Ca2+ sequestered in the endoplasmic reticulum.

Bile↗
PubMed1990

Effect of glutathione on the redox transitions of naphthohydroquinone derivatives formed during DT-diaphorase catalysis.

The oxidation of GSH coupled to the redox transitions of 1,4-naphthoquinone derivatives during DT-diaphorase catalysis was examined. The quinones studied included 1,4-naphthoquinone and its dimethoxy- and hydroxy derivatives and were selected according to their different ability to undergo nucleophilic addition with GSH and the dual effect of superoxide dismutase on hydroquinone autoxidation. GSH was oxidized to GSSG during the redox transitions of the above quinones, regardless of their substitution pattern. This effect was accompanied by an increase of total O2 consumption, indicating the ability of GSH to support quinone redox cycling. The values for the relationship [O2]consumed/[GSSG]formed were, with every quinone examined, above unity, thus pointing to the occurrence of autoxidation reactions other than those involved during GSSG formation. These results are discussed in terms of the functional group chemistry of the quinones and the thermodynamic properties of the reactions involved in the reduction of the semi- to the hydro-quinone by GSH.

Catalysis↗
PubMed1990

2,5-Di(tert-butyl)-1,4-benzohydroquinone--a novel mobilizer of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool.

Isolated hepatocytes and the isolated perfused rat liver have been used to study the alterations of cytosolic free Ca2+ concentration ([Ca2+]i) produced by 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), a potent inhibitor of hepatic microsomal Ca2+ sequestration (Moore, G.A., McConkey, D.J., Kass, G.E.N., O'Brien, P.J. and Orrenius, S. FEBS Lett., 224, 331-336), (1987). Addition of tBuBHQ to isolated hepatocytes caused a rapid increase in [Ca2+]i which was similar in magnitude to the [Ca2+]i elevation induced by the Ca2+ mobilizing hormone, vasopressin. In contrast with vasopressin which caused a Ca2+ transient, tBuBHQ elevated [Ca2+]i to a new steady state that was maintained for up to 15-20 min. When vasopressin was administered during the tBuBHQ-induced period of elevated [Ca2+]i, [Ca2+]i rapidly returned to basal levels. Similarly, if vasopressin was administered just prior to tBuBHQ, the resultant tBuBHQ-dependent change in [Ca2+]i was transient, and not sustained. The hydroquinone mobilized the same intracellular Ca2+ pool as inositol 1,4,5-trisphosphate, but tBuBHQ did not produce any detectable inositol polyphosphate accumulation. tBuBHQ stimulated glucose release from perifused hepatocytes, mimicking the effect of vasopressin. In the perfused liver, tBuBHQ infusion produced a single, slow and prolonged release of Ca2+ into the perfusate and inhibition of subsequent vasopressin-induced Ca2+ effluxes. Inhibition of the response to vasopressin was reversed over time, and closely correlated with the extent of inhibition of both Ca2+ sequestration and (Ca2+-Mg2+)-ATPase activity in microsomes isolated from the isolated perfused liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗