Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00035 (CSF)
 30,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CSF HCO3- increases more than plasma HCO3- in hypercapnia, and there are at least two sources for the CSF HCO3- increase--one derived from the simultaneous increase in plasma HCO3-, and the other, HCO3-formed from hydration of CO2 in the choroid plexus and glia and susceptible to inhibition by acetazolamide (J. Appl. Physiol. 38: 504-512, 1975). It was proposed that the H+ formed in the CNS in CO2 hydration is actively exchanged for plasma Na+ utilizing the Na-K ATPase pump. H+ transport from the CNS was therefore studied in four groups of dogs breathing 5% CO2 at constant VA for 4 h with repeated injections of saline, acetazolamide 5 mg/ml, ouabain 0.1 mg/ml, and acetazolamide and ouabain together into lateral cerebral ventricles. Arterial HCO3-increased 2.5 meq/l at 4 h of hypercapnia in all groups. CSF HCO3-increased 5.8 meq/l in the saline-injected animals, but it increased only about 2 meq/l and equaled plasma HCO3- rise in the other three groups. Therefore CNS HCO3- formation in hypercapnia can be blocked by inhibiting the CO2 hydration reaction with acetazolamide or by blocking H+ removal by inhibiting Na-K ATPase with ouabain. The data support the thesis of active H+ removal from the CNS in exchange for plasma Na+ in hypercapnia.
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PMID:H+ transport from CNS in hypercapnia and regulation of CSF [HCO3-]. 1 62

Infusions of isotonic or hypertonic (0.3 or 0.5 M) glycerol into the lateral cerebral ventricle (60 min, 0.02 ml/min) of non-hydrated goats invariably induced a conspicuous and sustained water diuresis. Corresponding infusions of 0.3 M glycerol/0.16 M NaCl were almost equally efficient in this respect. A more short-lasting and less pronounced water diuresis was obtained in response to equivalent infusions of pure d-glucose, and the response to 0.3 M glucose/0.16 M NaCl was variable. Intravenous injections of vasopressin blocked the glucose-induced diuresis, but only postponed the glycerol-induced diuresis. Intracerebroventricular (IVT) infusions of 0.5 M glycerol caused a sustained, complete inhibition of the urge to drink in the 48 h dehydrated goat, whereas IVT glucose only attenuated dehydrative drinking. Twenty min after the infusions of glycerol the CSF [Na+] in the lateral ventricle was about 15% below normal. About 10% reduction of CSF [Na+] was obtained 20 min after the IVT infusion of glycerol/NaCl. The corresponding infusion of pure d-glucose reduced the CSF [Na+] by less than 5%. The glycerol and glycerol/NaCl infusions caused a moderate reduction of renal Na+ + K+ excretion. The possibility is discussed that the observed effects of IVT glycerol is a manifestation of its efficiency to inhibit choroidal and/or juxtaventricular (Na+-K+)-ATPase activity.
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PMID:Intracerebroventricular glycerol: a potent inhibitor of ADH-release and thirst. 99 97

The effect of ventriculo-cisternal perfusion of ouabain was determined on CSF production after inhibition of carbonic anhydrase by benzolamide in cats. An additional decrease in CSF formation was observed by combination of i.v. benzolamide and intraventricular ouabain. However, the effect of the combined drugs was less than the sum of the effects of the drugs given individually. It is concluded that the reduction of the CSF production by ouabain is probably partly due to its effect on Na-K exchange (through inhibition of Na-K-activated ATPase) and partly due to its effects on Na+ transport coupled to anion transport mediated by carbonic anhydrase.
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PMID:Effect of ouabain on cerebrospinal fluid formation after carbonic anhydrase inhibition. 114 16

Magnesium is an essential cofactor for many enzymatic reactions, especially those involved in energy metabolism. Deficits of magnesium are prevalent due to inadequate intake or malabsorption and due to the renal loss of magnesium that occurs in certain disease states (alcoholism, diabetes) and with drug therapy (diuretics, aminoglycosides, cisplatin, digoxin, cyclosporin, amphotericin B). Protracted deficits of magnesium in humans and animals result in neurological disturbances, including hyperexcitability, convulsions and various psychiatric symptoms ranging from apathy to psychosis, some of which can be reversed with magnesium supplementation, others requiring correction of the dysregulation mechanism. Although the role of magnesium in neuronal function is not completely understood, a lowering of CSF or brain magnesium can induce epileptiform activity and there is an association between decreased CSF magnesium and the development of seizures. CSF concentrations of magnesium are normally higher than magnesium plasma ultrafiltrate (diffusible) concentrations due to the active transport of magnesium across the blood-brain barrier. Under conditions of magnesium deficiency, CSF concentrations decline, although this decline lags behind and is less pronounced than the changes observed in plasma magnesium concentrations. Decreases in CSF magnesium concentrations correlate with the alterations observed in extracellular brain magnesium concentrations in animals following the dietary deprivation of magnesium. CSF magnesium concentrations can readily be repleted following magnesium supplementation, although high dose magnesium therapy, such as that used in the treatment of convulsions in eclampsia, will only increase CSF magnesium concentrations to a very limited degree (approximately 11-18 per cent) above physiological concentrations. Greater increases in CSF magnesium may occur in neonates since neonatal swine, following treatment with magnesium, have CSF magnesium concentrations that are similar to their plasma concentrations. There has been a recent resurgence of interest in magnesium deficiency and its neurological consequences due to the finding that magnesium, at physiological concentrations, blocks N-methyl-D-aspartate (NMDA) receptors in neurones. NMDA receptors are normally activated by glutamate and/or aspartate which represent the principal neurotransmitters for excitatory synaptic transmission in vertebrate CNS. Magnesium deficiency produces epileptiform activity in the CNS which can be blocked by NMDA receptor antagonists. Other mechanisms, including alterations in Na+/K(+)-ATPase activity, cAMP/cGMP concentrations and calcium currents in pre- and postsynaptic membranes, may also be at least partially responsible for the neuronal effects associated with low brain magnesium. Further studies are necessary to increase our understanding of the neurological implications of magnesium deficit in the central nervous system.
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PMID:Brain and CSF magnesium concentrations during magnesium deficit in animals and humans: neurological symptoms. 129 67

Omeprazole, a specific inhibitor of H(+)-K(+)-activated ATPase, gave a dose-dependent inhibition of CSF production as determined by cerebroventriculocisternal perfusions in the rabbit. The reduction was 35% when the perfusate concentration of omeprazole was 10(-6) M and 25% after an intravenous dose of 0.2 mg/kg of omeprazole, respectively. A similarly substituted benzimidazol (H178/42) without H(+)-K(+)-ATPase-inhibiting properties did not affect CSF production at a perfusate concentration of 10(-5) M. Omeprazole in a concentration of 2 x 10(-4) M and more caused a significant but variable reduction in total and Na(+)-K(+)-ATPase activity in choroid plexus homogenates. However, in concentrations of 2 x 10(-5) M and less, no effect on total or Na(+)-K(+)-ATPase activity was obtained. Nor did omeprazole (2 x 10(-4) M) influence HCO3-ATPase. Choline uptake in isolated choroid plexus was significantly reduced by 86% in the presence of acid-pretreated omeprazole 2 x 10(-3) M, but was not affected by 2 x 10(-5) M omeprazole (intact or acid-pretreated). Thus, the mechanism for the marked inhibitory influence of omeprazole on CSF production is not yet evident. In doses causing even a 50% reduction of CSF production, no side effects were observed in contrast to Na(+)-K(+)-ATPase inhibitors such as ouabain.
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PMID:Inhibition of cerebrospinal fluid formation by omeprazole. 131 Dec 67

Lucifer yellow (LY) accumulation was used to measure macrophage pinocytosis. The hematopoietic growth factors, macrophage colony-stimulating factor (CSF-1), granulocyte-macrophage CSF (GM-CSF), and interleukin 3, and the macrophage activators, lipopolysaccharide and zymosan, all stimulated LY uptake in both murine bone marrow-derived macrophages (BMMs) and resident peritoneal macrophages (RPMs) without affecting LY efflux. The stimulation of pinocytosis in the poorly cycling RPMs and in BMMs by nonmitogens dissociates stimulation of pinocytosis from subsequent DNA synthesis. Regulation of pinocytosis in BMMs appears to be independent of that of urokinase-type plasminogen activator expression. The increases in CSF-mediated BMM pinocytosis were not inhibited by pertussis toxin, by elevations in intracellular cAMP, or by glucocorticoids and were only partially inhibited by inhibitors of Na+/H+ antiport and Na+/K(+)-ATPase activities. Protein kinase C activation could be involved in regulating BMM pinocytosis because phorbol myristate acetate, oleoylacyglycerol, and exogenously added phospholipase C can all stimulate it. Ca2+ ionophores were inactive, whereas the Na+/H+ ionophore monensin potently inhibited BMM pinocytosis.
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PMID:Regulation of pinocytosis in murine macrophages by colony-stimulating factors and other agents. 131 79

Bone resorption plays an important role in bone modeling and remodeling. Osteoclasts are the cells responsible for the bone resorption. Osteoclasts are located on endosteal bone surfaces and on the periosteal surface beneath the periosteum. They are multinucleated giant cells highly polarized in their morphology and function. Among the proximal surface, the membrane and the area of the cytoplasm directly oppose to the bone surface, which are specialized into two regions. A central region consisting of many irregular cytoplasmic processes and infoldings, the ruffled border, is known to be the active site of bone resorption. Surrounding the ruffled border, a second region, the clear zone provides an area of close attachment to the mineralized bone surface. The osteoclasts secrete a large amount of protons by the action of H(+)-pump on the ruffled border into the sealed resorption cavity, resulting in the acidified microenvironment under which condition the bone matrix is dissolved. Protons are provided by the intracellular action of carbonic anhydrase. Following the secretion of the protons, several ion-transporting systems, i.e., carbonate-chloride exchanger, chloride-channel, Ca(2+)-transport systems, Na+/K(+)-ATPase, and voltage-dependent Ca(2+)-channel, are sequentially operated on both apical and basolateral cytoplasmic membranes. In addition, osteoclasts contain a large amount of lysosomal enzymes (cathepsin C, beta-glycerophosphatase, beta-glucuronidase, etc.), which contribute to degrade the bone organic matrices exposed in the resorption cavity. These enzymes bind to the mannose-6-phosphate receptor on Golgi apparatus, are transported to the ruffled border and are secreted into the extracellular compartment in an exocytotic manner. Osteoclasts also have a high tartrate-resistant acid phosphatase activity which is currently used as a marker enzyme osteoclastic differentiation. Osteoclasts are considered to develop from hematopoietic stem cells. So far, the following four different pathways of the differentiation of osteoclast are proposed: The precursors of osteoclast develop (1) from multilineage hematopoietic cells via a completely separate differentiation line, (2) from granulocyte macrophage-colony forming cells, (3) from committed but proliferative monocyte-macrophage, and (4) from mature and unproliferative monocyte-macrophage. However, the differentiation line of the osteoclasts has still to be elucidated. The formation of osteoclasts as well as that of other hematopoietic cells is strongly regulated by many cytokines [interleukin (IL)-1,IL-3,IL-6, M-colony stimulating factor (CSF), and GM-CSF]. 1,25-Dihydroxyvitamin D3 and parathyroid hormone also stimulate the differentiation of osteoclast precursors. However, the mature osteoclasts do not possess the receptors for these hormones.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Osteoclasts in bone metabolism]. 175 56

Purified hematopoietic growth factors such as colony-stimulating factor-1 (CSF-1) or macrophage CSF, granulocyte-macrophage CSF, and interleukin-3 or multi-CSF, stimulate the urokinase-type plasminogen activator (u-PA) activity of murine bone marrow-derived macrophages (BMM) and resident peritoneal macrophages. Granulocyte-CSF was inactive. The increases in BMM u-PA activity were inhibited by the glucocorticoid dexamethasone, and by agents that raise intracellular cyclic adenosine monophosphate levels, including prostaglandin E2 and cholera toxin. These changes in u-PA activity were paralleled by corresponding changes in u-PA mRNA levels. Evidence was obtained for protein kinase C and phospholipase C-mediated stimulation of BMM u-PA activity and mRNA levels; however, no evidence was found for an involvement of Na+/H+ exchange or Na+, K(+)-ATPase activity, Ca2+ fluxes, or pertussis toxin-sensitive G proteins. Several findings point to a dissociation between macrophage u-PA expression and DNA synthesis.
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PMID:Activation and proliferation signals in murine macrophages. Biochemical signals controlling the regulation of macrophage urokinase-type plasminogen activator activity by colony-stimulating factors and other agents. 184 64

The calcium theory of neuronal damage has been recently adapted to subarachnoid haemorrhage (SAH). It is proposed that haemorrhagic insult to the brain causes free radical-mediated destructive reactions of membrane phospholipids, and the consequent decrease of phospholipid-dependent enzymatic activities, such as Na(+)-K+ ATPase. In the present study we have studied the effects of Nicardipine treatment on lipid peroxidation and Na(+)-K+ ATPase activity after experimental induction of SAH. SAH was induced in anaesthesized rats by slow injection of 0.3 ml of autologous arterial blood into the cisterna magna. We assessed the extent of lipid peroxidation by measuring the level of thiobarbituric acid reactive substances (TBARS) and Na(+)-K+ ATPase activity in 3 different rat brain areas (cerebral cortex, hippocampus and brain stem) of sham-operated (0.3 ml of mock CSF into cisterna magna) and at 1 hour, 6 hours and 48 hours after SAH induction; simultaneously, we investigated the capacity of cerebral lipid peroxidation by measuring the accumulation of TBRAS in homogenates of brain areas incubated under aerobic conditions. Na(+)-K+ ATPase activity decreased in the cerebral cortex at 1 hour and 6 hours and in brain stem at 1 hour after SAH, while the same enzymatic activity did not change in the hippocampus. There was no significant difference in lipid peroxide content between sham-operated and haemorrhagic animals; Nicardipine treatment reduced the TBRAS content and induced the recovery of Na(+)-K+ ATPase activity, exerting a brain protective role against the detrimental effects of the haemorrhage.
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PMID:Effects of nicardipine treatment on Na(+)-K+ ATPase and lipid peroxidation after experimental subarachnoid haemorrhage. 185 1

1. At thermoneutrality (28 degrees C), CSF Na+:Ca2+ in hens was 61.66; under thermal stress (39 degrees C), it changed to 59.38 (30 min), 62.58 (3 hr), and 52.44 (10 hr); no change in ratio occurred at 15 degrees C. 2. ICV Ouabain and/or EGTA increased body temperature (TR) but not respiration rate (RR) at 39 degrees C. 3. At 28 degrees C, Ouabain decreased, and EGTA increased, TR and RR. 4. Ca2+ may be more critical than Na+ in thermoregulation. 5. Heat stress appears to stimulate Na+-transport mechanisms other than Na+-ATPase. 6. RR appears to be a function of TR, not of ion balance.
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PMID:CSF ion composition and manipulation during thermoregulation in an avian species, Gallus domesticus. 197 30


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