SEARCH · PubMed Health

Results for “HOMEOSTASIS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources

PubMed2002

DL-Homocysteic acid application disrupts calcium homeostasis and induces degeneration of spinal motor neurons in vivo.

Excitotoxicity, autoimmunity and free radicals have been postulated to play a role in the pathomechanism of amyotrophic lateral sclerosis (ALS), the most frequent motor neuron disease. Altered calcium homeostasis has already been demonstrated in Cu/Zn superoxide dismutase transgenic animals, suggesting a role for free radicals in the pathogenesis of ALS, and in passive transfer experiments, modeling autoimmunity. These findings also suggested that yet-confined pathogenic insults, associated with ALS, could trigger the disruption of calcium homeostasis of motor neurons. To test the possibility that excitotoxic processes may also be able to increase calcium in motor neurons, we applied the glutamate analogue DL-homocysteic acid to the spinal cord of rats in vivo and analyzed the calcium distribution of the motor neurons over a 24-h survival period by electron microscopy. Initially, an elevated cytoplasmic calcium level, with no morphological sign of degeneration, was noticed. Later, increasing calcium accumulation was seen in different cellular compartments with characteristic features of alteration at different survival times. This calcium accumulation in organelles was paralleled by their progressive degeneration, which culminated in cell death by the end of the observation time. These findings confirm that increased calcium also plays a role in excitotoxic lesion of motor neurons, in line with previous studies documenting the involvement of calcium ions in motor neuronal injury in other models of the disease as well as elevated calcium in biopsy samples from ALS patients. We suggest that intracellular calcium might be responsible for the interplay between the different pathogenic processes resulting in a uniform clinicopathological picture of the disease.

Amyotrophic Lateral Sclerosis↗

PubMed2006

Telomere length homeostasis.

The physical ends of chromosomes, known as telomeres, protect chromosome ends from nucleolytic degradation and DNA repair activities. Conventional DNA replication enzymes lack the ability to fully replicate telomere ends. In addition, nucleolytic activities contribute to telomere erosion. Short telomeres trigger DNA damage checkpoints, which mediate cellular senescence. Telomere length homeostasis requires telomerase, a cellular reverse transcriptase, which uses an internal RNA moiety as a template for the synthesis of telomere repeats. Telomerase elongates the 3' ends of chromosomes, whereas the complementary strand is filled in by conventional DNA polymerases. In humans, telomerase is ubiquitously expressed only during the first weeks of embryogenesis, and is subsequently downregulated in most cell types. Correct telomere length setting is crucial for long-term survival. The telomere length reserve must be sufficient to avoid premature cellular senescence and the acceleration of age-related disease. On the other side, telomere shortening suppresses tumor formation through limiting the replicative potential of cells. In recent years, novel insight into the regulation of telomerase at chromosome ends has increased our understanding on how telomere length homeostasis in telomerase-positive cells is achieved. Factors that recruit telomerase to telomeres in a cell cycle-dependent manner have been identified in Saccharomyces cerevisiae. In humans, telomerase assembles with telomeres during S phase of the cell cycle. Presumably through mediating formation of alternative telomere structures, telomere-binding proteins regulate telomerase activity in cis to favor preferential elongation of the shortest telomeres. Phosphoinositide 3-kinase related kinases are also required for telomerase activation at chromosome ends, at least in budding and fission yeast. In vivo analysis of telomere elongation kinetics shows that telomerase does not act on every telomere in each cell cycle but that it exhibits an increasing preference for telomeres as their lengths decline. This suggests a model in which telomeres switch between extendible and nonextendible states in a length-dependent manner. In this review we expand this model to incorporate the finding that telomerase levels also limit telomere length and we propose a second switch between a non-telomerase-associated "extendible" and a telomerase-associated "extending" state.

Animals↗

PubMed1998

Effect of aluminum on cytoplasmic Ca2+ homeostasis in root hairs of Arabidopsis thaliana (L.).

Aluminum inhibition of root growth is a major world agricultural problem where the cause of toxicity has been linked to changes in cellular calcium homeostasis. Therefore, the effect of aluminum ions (Al) on changes in cytoplasmic free calcium concentration ([Ca2+]c) was followed in root hairs of wild-type, Al-sensitive and Al-resistant mutants of Arabidopsis thaliana (L.) Heynh. Generally, Al exposure resulted in prolonged elevations in tip-localized [Ca2+]c in both wild-type and Al-sensitive root hairs. However, these Al-induced increases in [Ca2+]c were not tightly correlated with growth inhibition, occurring up to 15 min after Al had induced growth to stop. Also, in 32% of root hairs examined growth stopped without a detectable change in [Ca2+]c. In contrast, Al-resistant mutants showed little growth inhibition in response to AlCl3 exposure and in no case was a change in [Ca2+]c observed. Of the other externally applied stresses tested (oxidative and mechanical stress), both were found to inhibit root hair growth, but only oxidative stress (H2O2, 10 microM) caused a prolonged rise in [Ca2+]c similar to that induced by Al. Again this increase occurred after growth had been inhibited. The lack of a tight correlation between Al exposure, growth inhibition and altered [Ca2+]c dynamics suggests that although exposure of root hairs to toxic levels of Al causes an alteration in cellular Ca2+ homeostasis, this may not be a required event for Al toxicity. The elevation in [Ca2+]c induced by Al also strongly suggests that the phytotoxic action of Al in root hairs is not through blockage of Ca2(+)-permeable channels required for Ca2+ influx into the cytoplasm.

Aluminum↗

PubMed1999

Lic4, a nuclear phosphoprotein that cooperates with calcineurin to regulate cation homeostasis in Saccharomyces cerevisiae.

The target of the immunosuppressants cyclosporin A(CsA) and FK506 is calcineurin, a highly conserved protein phosphatase that is required for T-cell activation and the regulation of ion homeostasis in yeast. Here we identify two genes, PMR2B and LIC4 which, when overexpressed, suppress the cation-sensitive phenotype of yeast cells lacking calcineurin. PMR2B encodes a Na+/Li+-specific plasma membrane pump and is similar to PMR2A, whose expression is known to be regulated by calcineurin. LIC4 (lithium comvertas) encodes a novel 33-kDa protein with no identity to known proteins. LIC4 overexpression suppresses the Li+-sensitive phenotype of calcineurin mutants but not the defect in recovery from pheromone arrest or viability of calcineurin dependent mutants, indicating a specific role in cation homeostasis. Similarly, lic4 mutations increase the Li+ sensitivity of both wild-type and calcineurin mutant strains, and reduce expression of pmr2A in calcineurin mutant strains, indicating that calcineurin and Lic4 may regulate parallel cation homeostatic pathways. lic4 mutations also exacerbate the Li+-sensitive phenotype of hal3 mutant strains, and overexpression of either Lic4 or Hal3 suppresses the salt sensitivity of mutant strains lacking calcineurin, Hal3, or Lic4, either singly or in combination. Taken together, these observations suggest that calcineurin, Hal3, and Lic4 cooperatively regulate the response of yeast cells to cation stress. Lic4 is phosphoprotein in vivo and a calcineurin substrate in vitro. By indirect and direct immunofluorescence detection of HA- and GFP-tagged proteins, Lic4 is localized in the nucleus in wild-type cells but predominantly cytoplasmic in cells lacking calcineurin. Taken together, our findings support a model in which calcineurin and Lic4 are components of signalling cascades that regulate cation stress responses in yeast.

Calcineurin↗

PubMed1998

Extraocular muscle in merosin-deficient muscular dystrophy: cation homeostasis is maintained but is not mechanistic in muscle sparing.

Extraocular muscle is uniquely spared from damage in merosin-deficient congenital muscular dystrophy. Using a murine model, we have tested the hypothesis that the maintenance of calcium homeostasis is mechanistic in extraocular muscle protection. Atomic absorption spectroscopy has demonstrated a strong correlation between the perturbation of calcium homeostasis in hindlimb muscle that is severely damaged and the absence of changes in calcium in extraocular muscle. If, as in other skeletal muscles, extraocular muscle fibers are destabilized by merosin deficiency, we would expect an increase in total muscle calcium coupled with an adaptive response in the high capacity/speed of the sarcoplasmic reticulum of the eye muscle. However, we have not observed the expected increases in total muscle calcium content, Ca2+-ATPase activity, Na+/Ca2+ exchanger content, or smooth ER Ca2+-ATPase content that are predicted by this model. Instead, these results indicate that the increased membrane permeability that characterizes, and is potentially mechanistic in, myofiber degeneration in muscular dystrophy does not occur in merosin-deficient extraocular muscle. Thus, the high-capacity calcium-scavenging systems are not primarily responsible for extraocular muscle protection in muscular dystrophy.

Animals↗

PubMed2006

Molecular and clinical aspects of iron homeostasis: From anemia to hemochromatosis.

The discovery in recent years of a plethora of new genes whose products are implicated in iron homeostasis has led to rapid expansion of our knowledge in the field of iron metabolism and its underlying complex regulation in both health and disease. Abnormalities of iron metabolism are among the most common disorders encountered in practical medicine and may have significant negative impact on physical condition and life expectancy. Basic insights into the principles of iron homeostasis and the pathophysiological and clinical consequences of iron overload, iron deficiency and misdistribution are thus of crucial importance in modern medicine. This review summarizes our current understanding of human iron metabolism and focuses on the clinically relevant features of hereditary and secondary hemochromatosis, iron deficiency anemia, anemia of chronic disease and anemia of critical illness. The interconnections between iron metabolism and immunity are also addressed, in as much as they may affect the risk and course of infections and malignancies.

Adolescent↗

PubMed2004

Both mercury and cadmium directly influence calcium homeostasis resulting from the suppression of scale bone cells: the scale is a good model for the evaluation of heavy metals in bone metabolism.

To examine the effects of heavy metals such as cadmium and mercury on calcium homeostasis, plasma calcium and calcitonin were measured in goldfish. Cadmium induced hypocalcemia both at 4 and at 8 days. In methylmercury-treated goldfish, the plasma calcium level increased at 2 days and then decreased at 8 days. The plasma calcitonin level increased in correspondence with the increased plasma calcium by methylmercury treatment, although cadmium did not cause a significant change. To elucidate the mechanism in detail, fish scales, which have both osteoclasts and osteoblasts and are similar to mammalian membrane bone, were used in the present study. We measured tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) activity as respective indicators of activity in both types of cells. TRAP activity in the scales decreased by treatment of cadmium and methylmercury at 6 h incubation. Particularly, cadmium (even at 10(-13) M) significantly suppressed TRAP activity, suggesting that this system is utilized as an acute biosensor for cadmium. ALP activity decreased after exposures of 64 and 96 h, although the activity did not change after 6, 18, and 36 h. In addition, mRNA expression of the estrogen receptor and insulin-like growth factor 1, which participate in osteoblastic growth and differentiation, was less than the control values by treatment with both metals. This study demonstrates that mercury directly acts on the bone cells and influences calcium homeostasis and indicates that, in a short-term exposure, mercury has a different action from that of cadmium and induces hypercalcemia.

Acid Phosphatase↗

PubMed1998

pH homeostasis and ATP synthesis: studies of two processes that necessitate inward proton translocation in extremely alkaliphilic Bacillus species.

Alkaliphilic Bacillus species that are isolated from nonmarine, moderate salt, and moderate temperature environments offer the opportunity to explore strategies that have developed for solving the energetic challenges of aerobic growth at pH values between 10 and 11. Such bacteria share many structural, metabolic, genomic, and regulatory features with nonextremophilic species such as Bacillus subtilis. Comparative studies can therefore illuminate the specific features of gene organization and special features of gene products that are homologs of those found in non-extremophiles, and potentially identify novel gene products of importance in alkaliphily. We have focused our studies on the facultative alkaliphile Bacillus firmus OF4, which is routinely grown on malate-containing medium at either pH 7.5 or 10.5. Current work is directed toward clarification of the characteristics and energetics of membrane-associated proteins that must catalyze inward proton movements. One group of such proteins are the Na+/H+ antiporters that enable cells to adapt to a sudden upward shift in pH and to maintain a cytoplasmic pH that is 2-2.3 units below the external pH in the most alkaline range of pH for growth. Another is the proton-translocating ATP synthase that catalyzes robust production of ATP under conditions in which the external proton concentration and the bulk chemiosmotic driving force are low. Three gene loci that are candidates for Na+/H+ antiporter encoding genes with roles in Na(+)-dependent pH homeostasis have been identified. All of them have homologs in B. subtilis, in which pH homeostasis can be carried out with either K+ or Na+. The physiological importance of one of the B. firmus OF4 loci, nhaC, has been studied by targeted gene disruption, and the same approach is being extended to the others. The atp genes that encode the alkaliphile's F1F0-ATP synthase are found to have interesting motifs in areas of putative importance for proton translocation. As an initial step in studies that will probe the importance and possible roles of these motifs, the entire atp operon from B. firmus OF4 has been cloned and functionally expressed in an Escherichia coli mutant that has a full deletion of its atp genes. The transformant does not exhibit growth on succinate, but shows reproducible, modest increases in the aerobic growth yields on glucose as well as membrane ATPase activity that exhibits characteristics of the alkaliphile enzyme.

Adenosine Triphosphate↗

PubMed2003

Combined effects of PPARgamma2 P12A and PPARalpha L162V polymorphisms on glucose and insulin homeostasis: the Québec Family Study.

Peroxisome proliferator-activated receptors gamma2 and alpha are nuclear factors known to be important regulators of lipid and glucose metabolism. Two polymorphisms, namely PPARgamma2 P12A and PPARalpha L162V, were investigated for their individual and interaction effects on glucose and insulin homeostasis. Genotypes were determined in 663 nondiabetic adults participating in the Québec Family Study and who underwent an oral glucose tolerance test (OGTT). The insulin and C-peptide areas under the curve (AUC) following the OGTT were higher in subjects carrying the PPARalpha V162 allele compared to homozygous for the L162 allele. When subjects were grouped according to both polymorphisms, higher levels of insulin and C-peptide during the OGTT were observed for those carrying the PPARalpha V162 allele except when they carry at the same time the PPARgamma2 A12 allele. Thus, the PPARgamma2 A12 allele seems protective against the deleterious effect of the PPARalpha V162 allele. Furthermore, a significant gene-gene interaction was observed for the acute (0-30 min) (p<0.001) and the total (p=0.05) C-peptide AUC following the OGTT. These results provide evidence of a gene-gene interaction in the regulation of plasma glucose-insulin homeostasis, and emphasize that these interactions need to be taken into account when dissecting the genetic etiology of complex disorders.

Adult↗

PubMed1999

Volatile anesthetic action on muscle Ca2+ homeostasis.

It is proposed that volatile anesthetics act through the modification of Ca2+ homeostasis in excitable cells. To test this hypothesis, cardiac and skeletal muscles were used as models to examine Ca2+ response, and Ca2+ regulatory and delivery mechanisms. I found that halothane did not alter Ca2+ binding to cardiac troponin C. However, halothane and isoflurane reversibly decreased the Ca2+ affinity of calmodulin at low anesthetic concentration, and irreversibly increased the Ca2+ affinity of calmodulin at high anesthetic concentration. The volatile anesthetics also increased the permeability of light fraction of sarcoplasmic reticulum (SR) to Ca2+. I conclude that volatile anesthetics alter calcium homeostasis in cardiac and skeletal muscles. This work was in part performed in collaboration with Giovanni Salviati and the author benefited from Salviati's work in similar areas.

Anesthetics, Inhalation↗

PubMed2006

Multi-scale computational model of fuel homeostasis during exercise: effect of hormonal control.

A mathematical model of the whole-body metabolism is developed to predict fuel homeostasis during exercise by using hormonal control over cellular metabolic processes. The whole body model is composed of seven tissue compartments: brain, heart, liver, GI (gastrointestinal) tract, skeletal muscle, adipose tissue, and "other tissues". Each tissue compartment is described by dynamic mass balances and major cellular metabolic reactions. The glucagon-insulin controller is incorporated into the whole body model to predict hormonal changes during exercise. Moderate [150 W power output at 60% of peak oxygen consumption (VO(2max))] exercise for 60 min was implemented by increasing ATP utilization rates in heart and skeletal muscle. Arterial epinephrine level was given as an input function, which directly affects heart and skeletal muscle metabolism and indirectly other tissues via glucagon-insulin controller. Model simulations were validated with experimental data from human exercise studies. The exercise induced changes in hormonal signals modulated metabolic flux rates of different tissues in a coordinated way to achieve glucose homeostasis, demonstrating the efficacy of hormonal control over cellular metabolic processes. From experimental measurements of whole body glucose balance and arterial substrate concentrations, this model could predict the dynamic changes of hepatic glycogenolysis and gluconeogenesis, which are not easy to measure experimentally, suggesting the higher contribution of glycogenolysis ( approximately 75%). In addition, it could provide dynamic information on the relative contribution of carbohydrates and lipids for fuel oxidation in skeletal muscle. Model simulations indicate that external fuel supplies from other tissue/organ systems to skeletal muscle become important for prolonged exercise emphasizing the significance of interaction among tissues. In conclusion, this model can be used as a valuable complement to experimental studies due to its ability to predict what is difficult to measure directly, and usefulness to provide information about dynamic behaviors.

Adaptation, Physiological↗

PubMed2006

The RcnRA (YohLM) system of Escherichia coli: a connection between nickel, cobalt and iron homeostasis.

The transporter RcnA has previously been implicated in Ni(II) and Co(II) detoxification in E. coli probably through efflux. Here we demonstrate that the divergently described rcnA and rcnR gene products constitute a link between nickel, cobalt and iron homeostasis. Deletion of the rcnA gene resulted in increased cellular nickel, cobalt and iron concentrations. Expression of rcnA was induced by Ni(II) or Co(II). Overproduction of rcnR inhibited induction of rcnA by metal cations but RcnR did not bind to the rcnA promoter in vitro. When rcnR or fur, the gene of the global repressor of iron homeostasis, was deleted, expression of rcnA was also induced by iron. The promoter region of rcnA was positive in a Fur titration (FURTA) in vivo assay indicative of Fur binding. Thus, rcnA is part of the Fur regulon of E. coli. The implications of a connection between the homoeostasis of closely related transition metals are discussed.

Bacterial Proteins↗

PubMed2006

The effect of nimodipine on calcium homeostasis and pain sensitivity in diabetic rats.

1. The pathogenesis of diabetic neuropathy is a complex phenomenon, the mechanisms of which are not fully understood. Our previous studies have shown that the intracellular calcium signaling is impaired in primary and secondary nociceptive neurons in rats with streptozotocin (STZ)-induced diabetes. Here, we investigated the effect of prolonged treatment with the L-type calcium channel blocker nimodipine on diabetes-induced changes in neuronal calcium signaling and pain sensitivity. 2. Diabetes was induced in young rats (21 p.d.) by a streptozotocin injection. After 3 weeks of diabetes development, the rats were treated with nimodipine for another 3 weeks. The effect of nimodipine treatment on calcium homeostasis in nociceptive dorsal root ganglion neurons (DRG) and substantia gelatinosa (SG) neurons of the spinal cord slices was examined with fluorescent imaging technique. 3. Nimodipine treatment was not able to normalize elevated resting intracellular calcium ([Ca(2+)]( i )) levels in small DRG neurons. However, it was able to restore impaired Ca(2+) release from the ER, induced by either activation of ryanodine receptors or by receptor-independent mechanism in both DRG and SG neurons. 4. The beneficiary effects of nimodipine treatment on [Ca(2+)]( i ) signaling were paralleled with the reversal of diabetes-induced thermal hypoalgesia and normalization of the acute phase of the response to formalin injection. Nimodipine treatment was also able to shorten the duration of the tonic phase of formalin response to the control values. 5. To separate vasodilating effect of nimodipine Biessels et al., (Brain Res. 1035:86-93) from its effect on neuronal Ca(2+) channels, a group of STZ-diabetic rats was treated with vasodilator - enalapril. Enalapril treatment also have some beneficial effect on normalizing Ca(2+) release from the ER, however, it was far less explicit than the normalizing effect of nimodipine. Effect of enalapril treatment on nociceptive behavioral responses was also much less pronounced. It partially reversed diabetes-induced thermal hypoalgesia, but did not change the characteristics of the response to formalin injection. 6. The results of this study suggest that chronic nimodipine treatment may be effective in restoring diabetes-impaired neuronal calcium homeostasis as well as reduction of diabetes-induced thermal hypoalgesia and noxious stimuli responses. The nimodipine effect is mediated through a direct neuronal action combined with some vascular mechanism.

Animals↗

PubMed2001

Application of new methods and analytical approaches to research on polyunsaturated fatty acid homeostasis.

New methods and analytical approaches are important to challenge and/or validate established beliefs in any field including the metabolism of polyunsaturated fatty acids (PUFA; polyunsaturates). Four methods that have recently been applied toward obtaining a better understanding of the homeostasis of PUFA include the following: whole-body fatty acid balance analysis, magnetic resonance imaging (MRI), 13C nuclear magnetic resonance (NMR) spectroscopy, and gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Whole-body balance studies permit the measurement of both the percentage of oxidation of linoleate and alpha-linolenate and their conversion to long-chain PUFA. This method has shown that beta-oxidation to CO2 is normally the predominant metabolic fate of linoleate and alpha-linolenate. Furthermore, models of experimental undernutrition in both humans and animals show that beta-oxidation of linoleate and alpha-linolenate markedly exceeds their intake, despite theoretically sufficient intake of linoleate or alpha-linolenate. Preliminary results suggest that by using MRI to measure body fat content, indirect whole-body linoleate balance can be done in living humans. 13C NMR spectroscopy provided unexpected evidence that linoleate and alpha-linolenate were metabolized into lipids synthesized de novo, an observation later quantified by tracer mass balance done using GC-C-IRMS. This latter method showed that within 48 h of dosing with 13C-alpha-linolenate, >80% underwent beta-oxidation to CO2 by suckling rats, whereas 8-9% was converted to newly synthesized lipids and <1 % to docosahexaenoate. Further application of these recently developed methods in different models should clarify the emerging importance of beta-oxidation and carbon recycling in PUFA homeostasis in mammals including humans.

Animals↗

PubMed1990

Effects of the sulfonylureas on muscle glucose homeostasis.

The sulfonylureas have pharmacologic effects both on insulin secretion by pancreatic beta cells and on responsiveness to insulin in peripheral tissues. The effects of the sulfonylureas on skeletal muscle may have a particularly significant influence on glucose homeostasis because of the important role of muscle as a peripheral site of glucose clearance. Under most physiologic conditions, the rate-limiting step for glucose utilization in muscle is its uptake across the plasma membrane; for this reason, the effects of the sulfonylureas on glucose transport have been a focus for study. In muscle tissue, the sulfonylureas appear to augment the stimulation of glucose uptake by insulin but not to alter glucose homeostasis in the absence of insulin. The mechanism of this effect, which requires several hours of exposure to a sulfonylurea, has not been defined. Although studies with cultured muscle cells have yielded inconsistent findings, recent work with the L6 rat skeletal muscle cell line demonstrated that the sulfonylureas exerted effects similar to those in muscle tissue both in time course and in requirement for co-stimulation by insulin. Mechanistic studies in L6 cells have shown that the sulfonylureas induce increased glucose transporter messenger ribonucleic acid levels and increased total cellular content of transporter proteins even in the absence of insulin, but that insulin is required for augmented glucose uptake activity. Based on these data, it has been suggested that insulin may cause the activation of transporters synthesized in response to sulfonylureas. The definition of the mechanism of this synergistic response to insulin and the sulfonylureas in L6 muscle cells may give insight into the in vivo molecular events involved in the action of the sulfonylureas in skeletal muscle.

Animals↗

PubMed1993

Early pregnancy changes in hemodynamics and volume homeostasis are consecutive adjustments triggered by a primary fall in systemic vascular tone.

OBJECTIVE: The purpose of this study was to test the hypothesis that early pregnancy changes in volume homeostasis develop as a consequence of preceding changes in maternal hemodynamics. STUDY DESIGN: Maternal cardiovascular function of 10 pregnant women was followed up by Doppler echocardiography. Vascular filling state and volume homeostasis were evaluated by echocardiographic index values, glomerular filtration rate, serum osmolality, and volume-regulating hormones. Studies were performed weekly in early pregnancy, in the second and third trimesters, and post partum. Changes relative to the fifth week and the consistency of changes between weeks 5 and 8 were evaluated by nonparametric statistics. RESULTS: In early pregnancy cardiac output increased and afterload decreased. Concomitant increases in ultrasonic preload index values and glomerular filtration rate were accompanied by decreases in serum renin, Na+, and osmolality. CONCLUSION: These data support the concept that maternal hemodynamic adaptation to pregnancy is most likely triggered by a primary fall in systemic vascular tone. The resulting rapid fall in preload and afterload leads to a compensatory increase in heart rate and activation of the volume-restoring mechanisms. Subsequently cardiac output increases because of a rise in stroke volume, which develops because the vascular filling state normalizes, whereas the reduced afterload reduction is maintained.

Adult↗

PubMed1986

Inhibition of macrophage secretion by tetanus toxin is not directly linked to cytosolic calcium homeostasis.

Tetanus toxin (TT) inhibits secretion of neurotransmitters from neurons and lysozyme from human macrophages (Mphi). Because these secretory events are associated with changes in cytosolic free calcium [Ca2+]i, we examined the effect of TT on Mphi calcium homeostasis and secretion in response to ionomycin and phorbol myristate acetate (PMA). Using Quin 2 to report [Ca2+]i, basal [Ca2]i was similar for control cells (133 nM) and Mphi treated with TT (127 nM). In response to ionomycin (50 nM) [Ca2+]i increased to 548 +/- 74 nM in control cells and to 357 +/- 36 nM in TT-treated Mphi (p less than 0.02, N = 12). Despite this rise in [Ca2+]i, neither control Mphi nor TT-treated Mphis secreted the lysosomal enzyme lysozyme in response to this concentration of ionomycin (50 nM). In both control and TT-treated Mphi, stimulation with a higher concentration of ionomycin (1000 nM) caused saturation of the quin 2 fluorescence signal. However, lysozyme secretion from TT-Mphi was inhibited. In response to the phorbol ester, PMA (3 uM), [Ca2+]i did not increase in either control Mphi or TT-treated Mphi. However, secretion of lysozyme from TT-treated Mphi was also inhibited in response to this stimulus (70.8% of control, p less than 0.02, N = 3). These data indicate that the ability of TT to inhibit secretion from Mphi is not directly linked to alterations of cytosolic calcium homeostasis.

Aminoquinolines↗

PubMed1990

Ethanol and synaptosomal calcium homeostasis.

The effect of ethanol on synaptosomal calcium homeostasis was studied in the rat using the fluorescent dye, fura-2, and 45Ca uptake. The mitochondrial poison, cyanide, caused a substantial rise in intracellular free Ca2+ concentration, [Ca2+]i, over that of control synaptosomes. This rise was enhanced by ethanol. Ethanol also augmented the rise in [Ca2+]i induced by ouabain, indicating that modulation of Na(+)-Ca2+ exchange is probably not the underlying mechanism. The Ca2+ channel blockers, verapamil and La3+, also failed to inhibit the rise in [Ca2+]i caused by ethanol. Preincubation of synaptosomes with caffeine, however, caused a significant decrease in the rise of [Ca2+]i due to ethanol, suggesting that ethanol exerts effects on Ca2+ homeostasis at the level of the endoplasmic reticulum.

Animals↗