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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: We examined the effects of orally administered 5′-cytidinediphosphocholine (CDP-choline) on arterial plasma choline and cytidine levels and on brain phospholipid composition in rats. Animals receiving a single oral dose of 100, 250, or 500 mg/kg showed peak plasma choline levels 6–8 h after drug administration (from 12 ± 1 to 17 ± 2, 19 ± 2, and 24 ± 2 µM, respectively). The area under the plasma choline curve at 〉14 µM, i.e., at a concentration that induces a net influx of choline into the brain, was significantly correlated with CDP-choline dose. In rats receiving 500 mg/kg this area was 2.3 times that of animals consuming 250 mg/kg, which in turn was 1.8 times that of rats receiving 100 mg/kg. Plasma cytidine concentrations increased 5.4, 6.5, and 15.1 times baseline levels, respectively, 8 h after each of the three doses. When the oral CDP-choline treatment was prolonged for 42 and 90 days, brain phosphatidylcholine concentrations increased significantly (by 22–25%; p 〈 0.05) in rats consuming 500 mg/kg/day. Brain phosphatidylethanolamine and phosphatidylserine concentrations also increased significantly under some experimental conditions; levels of other phospholipids were unchanged.
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 64 (1995), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Using rat striatal slices, we examined the effect of cytidine on the conversion of [3H]choline to [3H]-phosphatidylcholine ([3H]PC), and on net syntheses of PC, phosphatidylethanolamine (PE), and phosphatidylserine, when media did or did not also contain choline, ethanolamine, or serine. Incubation of striatal slices with cytidine (50–500 µM) caused dose-dependent increases in intracellular cytidine and cytidine triphosphate (CTP) levels and in the rate of incorporation of [3H]choline into membrane [3H]PC. In pulse-chase experiments, cytidine (200 µM) also increased significantly the conversion of [3H]choline to [3H]PC during the chase period. When slices were incubated with this concentration of cytidine for 1 h, small (7%) but significant elevations were observed in the absolute contents (nmol/mg of protein) of membrane PC and PE (p 〈 0.05), but not phosphatidylserine, the synthesis of which is independent of cytidine-containing CTP. Concurrent exposure to cytidine (200 µM) and choline (10 µM) caused an additional significant increase (p 〈 0.05) in tissue PC levels beyond that produced by cytidine alone. Exposure to choline alone at a higher concentration (40 µM) increased the levels of all three membrane phospholipids (p 〈 0.01); the addition of cytidine, however, did not cause further increases. Concurrent exposure to cytidine (200 µM) and ethanolamine (20 µM) also caused significantly greater elevations (p 〈 0.05) in tissue PE levels than those caused by cytidine alone. In contrast, the addition of serine (500 µM) did not enhance cytidine's effects on any membrane phospholipid. Exposure to serine alone, however, like exposure to sufficient choline, increased levels of all three membrane phospholipids significantly (p 〈 0.01). These data show that exogenous cytidine, probably acting via CTP and the Kennedy cycle, can increase the synthesis and levels of membrane PC and PE in brain cells.
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 32 (2005), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. In the present study, we aimed to determine the involvement of brain thromboxane A2 (TXA2) in blood pressure decreases evoked by acute and/or graded haemorrhage in rats.2. Sprague-Dawley rats were used throughout the study. Acute haemorrhage was achieved by withdrawing a total volume of 2.1 and 2.5 mL blood/100 g bodyweight over a period of 10 min. A microdialysis study was performed in a hypothalamic area to measure extracellular TXA2 levels. Graded haemorrhage was conducted successively by withdrawing carotid arterial blood (0.55 mL/100 g bodyweight) over a 10 s period four times (S1–S4) at 5 min intervals. Furegrelate (125, 250 and 500 µg), a TXA2 synthase inhibitor, was injected intracerebroventricularly (i.c.v.) 60 min before acute or graded haemorrhage was initiated. U-46619 (0.5, 1 and 2 µg, i.c.v.), a synthetic TXA2 analogue, was administered 5 min before acute haemorrhage (2.1 mL/100 g bodyweight).3. Acute haemorrhage produced a severe and long-lasting decrease in blood pressure and had a tendency to increase heart rate. Both haemorrhage protocols (2.1 or 2.5 mL/100 g) generated similar approximate twofold increases in extracellular hypothalamic TXA2 levels. Intracerebroventricular furegrelate (250 µg) pretreatment completely blocked the TXA2 increases induced by acute haemorrhage. Furegrelate administration (100, 250 and 500 µg, i.c.v.) attenuated the fall in arterial pressure evoked by acute haemorrhage and caused significant increases in heart rate at all doses injected.4. Graded haemorrhage progressively lowered arterial pressure and increased plasma vasopressin and adrenaline levels in the last period. Furegrelate-injected rats were greatly resistant to the hypotensive effect of haemorrhage for all degrees of blood removed. Plasma adrenaline and vasopressin levels were significantly elevated in furegrelate-pretreated rats compared with the saline-treated group during S2–S3 and S4, respectively. U-46619 administration caused small but statistically significant decreases in arterial pressure induced by haemorrhage.4. The results show that acute hypotensive haemorrhage increases extracellular hypothalamic TXA2 levels. The increase in brain endogenous TXA2 levels involves a decrease in blood pressure evoked by haemorrhage because the blockade of TXA2 synthesis by furegrelate pretreatment attenuated the haemorrhagic hypotension. Increases in plasma adrenaline and vasopressin levels may mediate this effect.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Neurochemical research 23 (1998), S. 733-741 
    ISSN: 1573-6903
    Keywords: Choline ; acetylcholine ; vasopressin ; blood pressure ; hypotension ; spinal shock
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intracerebroventricular (i.c.v.) choline (50–150 μg) increased blood pressure and decreased heart rate in spinal cord transected, hypotensive rats. Choline administered intraperitoneally (60 mg/kg), also, increased blood pressure, but to a lesser extent. The pressor response to i.c.v. choline was associated with an increase in plasma vasopressin. Mecamylamine pretreatment (50 μg; i.c.v.) blocked the pressor, bradycardic and vasopressin responses to choline (150 μg). Atropine pretreatment (10 μg; i.c.v.) abolished the bradycardia but failed to alter pressor and vasopressin responses. Hemicholinium-3 [HC-3 (20 μg; i.c.v.)] pretreatment attenuated both bradycardia and pressor responses to choline. The vasopressin V1 receptor antagonist, (β-mercapto-β, β-cyclopenta-methylenepropionyl1, O-Me-Tyr2, Arg8)-vasopressin (10 μg/kg) administered intravenously 5 min after choline abolished the pressor response and attenuated the bradycardia-induced by choline. These data show that choline restores hypotension effectively by activating central nicotinic receptors via presynaptic mechanisms, in spinal shock. Choline-induced bradycardia is mediated by central nicotinic and muscarinic receptors. Increase in plasma vasopressin is involved in cardiovascular effects of choline.
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