PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Cytidine Diphosphate”

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 37 records · Page 2Linked to original sources

Biosynthesis of cytidine diphosphate diglyceride by human platelets.

Homogenates of human platelets contain an enzyme which catalyzes the formation of cytidine diphosphate diglyceride from cytidine triphosphate and phosphatidic acid. The enzymatic activity could not be dissociated from platelet particles and the greatest specific activity was found in the membrane fraction. The K(m) for cytidine triphosphate was 0.16 mmole/liter and the apparent K(m) for phosphatidic acid was 6.2 mmoles/liter. The pH optimum was 7.0 and the most effective buffers were triethanolamine-HCl and Tris-HCl. The reaction was dependent on the presence of divalent cations, magnesium being the most effective of those investigated. Monovalent cations did not alter the reaction rate. Evidence is presented that the cytidine diphosphate diglyceride produced can serve as a precursor for the synthesis of phosphatidylinositol. No difference was found in the enzymatic activity in platelets from normal subjects and from patients with diseases known to interfere with platelet thromboplastic function.

Blood Platelet Disorders↗

Biosynthesis of retinal phospholipids: incorporation of radioactivity from labeled phosphorylcholine and cytidine diphosphate choline.

Phosphorylcholine-1,2-(14)C and choline-1,2-(14)C-labeled cytidine diphosphate choline are incorporated into lecithin by whole homogenates and particulate fractions of rat retina with optimal incorporation of label by the microsomal fraction. The soluble fraction contains a factor(s) which stimulates incorporation of label with release of inorganic phosphate. Mg(++) is required for optimal incorporation of intermediates into lecithin in the presence of added diglycerides; without added diglycerides, incorporation of phosphorylcholine or cytidine diphosphate choline was moderately stimulated by preincubating the system in the absence of Mg(++) with added phosphatidic acid and by adding this mixture to fresh enzyme and the complete incubation mixture (including Mg(++)). The results show that the retina is capable of de novo synthesis of phosphatides and suggest that the rod outer segments depend on the pigment epithelium and(or) the inner rod segments for a source of phospholipids. Coenzyme A and ATP added to whole homogenate of retina did not significantly increase the incorporation of CDP-choline-1,2-(14)C into lecithin but slightly increased the radioactivity found in lysolecithin and sphingomyelin. Rats with hereditary retinitis pigmentosa have an abnormally high lipid phosphorus content of the retina, but they do not incorporate labeled CDP-choline into lecithin of retina at a higher rate than do normal animals.

Adenosine Triphosphate↗

Effects of cytidine diphosphate choline on rats with memory deficits.

The effects of cytidine diphosphate choline (CDP-choline, CAS 987-78-0) on learning and memory in rats with memory deficits were examined using behavioral methods of active avoidance with punishment reinforcement (shuttle-box), passive avoidance with punishment reinforcement (step-through and step-down), and active avoidance with positive (alimentary) reinforcement (staircase-maze). In the majority of experiments CDP-choline was applied orally at doses of 10-50 or 100 mg/kg daily for 7 days before the training session. The experiments were carried out on young-adult (aged 5 months) and old (aged 22 months) rats and on rats with a low capability for retention of learned behavior. Memory deficits were induced by the muscarinic cholinoceptor antagonist scopolamine (in young and old rats and mice), by the alpha 2-adrenoceptor agonist clonidine, by electroconvulsive shock, and by hypoxy. Memory deficits were also induced in rats offspring of dams that had been exposed to alcohol during pregnancy and lactation. The results suggest that CDP-choline acts as a memory-enhancing drug and that its effect is particularly pronounced in animals with memory deficits.

Aging↗

Biosynthesis of cytidine diphosphate diglyceride by enzyme preparations from cauliflower.

The activity of the enzyme responsible for the synthesis of cytidine diphosphate diglyceride has been found in the 20,000g pellet of a cauliflower (Brassica oleracea) inflorescence homogenate. Greater enzyme activity was found in the pellet after treatment with 0.02% Triton X-100, or after freezing and thawing. Activity was greater when fluoride was included in the reaction mixture. The enzyme has a pH optimum of 5.6, an optimal Mn(2+) concentration of 1mm and an optimal Mg(2+) concentration of 30 mm. At the optimal concentration, Mn(2+) was 4 times better than Mg(2+). The utilization of biosynthesized cytidine diphosphate diglyceride can be enhanced by addition of inositol, thereby causing the formation of phosphatidyl inositol.

Journal Article↗

Intestinal absorption of cytidine diphosphate choline and its changes in the digestive tract.

Intestinal absorption of cytidine diphosphate choline (CDP-choline), its structural changes in the digestive tract, and hepatic uptake have been investigated in rats using 14C-labeled (14CH3 attached to N of choline) and 3H-labeled (at C5 of pyrimidine) compounds. The results indicate that: 1)CDP-choline is relatively stable in the stomach, but is quickly degraded into cytidine and choline in the intestine; 2) The hepatic uptakes of 14C and 3H reach the maximum in two to three hours after oral administration; 3) Whereas the amount of 14C remaining in the gut is inversely related to the hepatic uptake, no similar correlation is seen with 3H-labeled CDP-choline, and 4) Extrahepatic uptake of 14C and 3H is very small. The possibility of phosphorylation in the mucosa of choline and cytidine has been discussed, based on the differences in individual broken-down products in the intestinal lumen and mucosa.

Animals↗

Long-term citicoline (cytidine diphosphate choline) use in patients with vascular dementia: neuroimaging and neuropsychological outcomes.

BACKGROUND: Cytidine diphosphate choline (citicoline) has been previously shown to have efficacy in reducing the functional impairments associated with acute stroke. Citicoline is thought to have neuroprotective benefits and has been used for the treatment of chronic cerebrovascular disorders, though its effectiveness has not been fully tested. This randomized, double-blind clinical trial was conducted to determine whether daily citicoline treatment improves neurocognitive and neuroimaging outcome over 12 months among patients diagnosed with vascular dementia (VaD). METHODS: 30 patients diagnosed with VaD, based upon NINDS-AIREN and DSM-IV criteria, were randomized and treated with either 500 mg of citicoline or placebo twice per day. Patients were assessed at baseline, and at 6, and 12 months on a battery of neurocognitive tests. Neuroimaging measures of total brain volume and subcortical/periventricular hyperintensity (SH) volume on magnetic resonance imaging (MRI) were collected at baseline and the 12-month follow-up. RESULTS: The citicoline and placebo treatment groups did not differ in their neuropsychological performance at baseline and the 12-month follow-up. Significant declines in neuropsychological performance were noted, as well as significantly increased SH and reduced total brain volumes on MRI for both groups at the 12-month follow-up. CONCLUSIONS: The efficacy of long-term citicoline treatment for cognitive impairment and neuropathological decline in those patients already meeting criteria for VaD does not appear to be substantiated by the current study.

Aged↗

Effect of cytidine diphosphate choline on growth hormone and prolactin secretion in man.

The effect of intravenous infusion of cytidine diphosphate choline (CDP-choline) on the serum levels of growth hormone (GH) and prolactin (PRL) was studied in six normal adult male subjects. Serum GH levels increased and reached a maximum at 60--90 min after the initiation of infusion in all subjects examined. The mean peak value of GH in six subjects was 10.0 +/- 2.1 (mean +/- SE) ng/ml, which was signigicantly higher than the basal level (p less than 0.01). In four subjects, serum PRL levels decreased from 10--24 ng/ml to less than 7.2 ng/ml at 60--120 min, while in the other two no significant change was observed. These results indicate that CDP-choline affects GH and PRL secretion from the anterior pituitary.

Adolescent↗

Enzymatic synthesis of cytidine diphosphate diglyceride.

Evidence is presented for the enzymatic formation of cytidine diphosphate diglyceride in microsomal preparations from guinea pig liver according to the reaction: CTP + phosphatidic acid right harpoon over left harpoon CDP-diglyceride + p-O-P. Conditions have been found in which the incorporation of labeled CTP into CDP-diglyceride is almost entirely dependent upon added phosphatidic acid. The incorporation of CMP into lipid is very slight. A substantial net synthesis of CDP-diglyceride takes place under these conditions. Some properties of the enzyme system are described.

Animals↗

Morphological effects of cytidin-diphosphate-choline on rats with lesions of the substantia nigra: study using horse radish peroxidase method.

Morphological effects of Cytidin-diphosphate-Choline (CDP-choline) (Ni-cholin) on rat brain with Substantia nigra lesions were studied by using the horse radish peroxidase method (HRP). Three groups of animals were studied. Post-lesion axonal and cellular regeneration was detected only in the group of rats treated with CDP-choline q.d. i.m. for 15 days.

Animals↗

Clinical trial on the use of cytidine diphosphate choline in Parkinson's disease.

Thirty patients with Parkinson's disease, treated with levodopa for the past few years, concomitantly received 500 mg of cytidine diphosphate choline (CDPC) daily for 30 days. Significant improvements in some of the neurologic signs and in several electrophysiologic parameters measuring the traction reflex and the active contraction were observed. A greater stability of therapeutic response between doses of levodopa was also seen, although the incidence of dyskinesia increased. In a second stage of CDPC treatment, also lasting 30 days, the dose of levodopa was reduced by one-third, and the incidence of dyskinesia dropped to its previous level, but the therapeutic response remained stable. Addition of CDPC produced significant increases in plasma concentrations of dopa and homovanillic acid, with no modifications in tyrosine or 3-O-methyldopa concentrations. A significant increase in the number of lymphocytic dopaminergic receptors also occurred.

Choline↗

Increase of survival time in experimental hypoxia by cytidine diphosphate choline.

36 Wistar rats were kept in chronic hypoxic hypoxia of 7 vol % of oxygen in 2 experiments over a period of 6 months, other 36 served as controls. Half of the animals of each group received cytidine diphosphate choline (CDP-choline, citicoline, Somazina; CAS 987-78-0) at a dose of 100 mg/kg body weight in the liquid food. Animals in chronic hypoxia without application of CDP-choline developed pathological symptoms and began to die after 19 to 23 weeks in hypoxia. Rats that received CDP-choline developed less prominent pathological symptoms and died later or remained alive until the end of the experiment. Under conditions of extreme hypoxia CDP-choline exhibited a life-prolonging effect.

Animals↗

Effect of cytidine diphosphate choline on anoxia tolerance of cultured myocardial cells.

Three series of cultured Wistar rat heart cells (10 treated and 10 controls x 3) were examined with a laser contraction-meter in a special chamber for anoxia to determine whether cytidine diphosphate choline (CDPC), a membrane phospholipid precursor, can protect against total oxygen deprivation. Heart rate and force of contraction (inotropism) were monitored during a 40-minute period of hypoxia. CDPC in a concentration of 142 micrograms/ml-1 was added to the culture medium only during the anoxia period in series I, during the 3 days of culture in series II, and during the 3 days of culture and the 40-minute hypoxia period in series III. In series I, inotropism decreased by 21% versus 55% in control group (P less than 0.05). In series II, inotropism decreased by 25% versus 43% in control group (P less than 0.05). In series III, inotropism decreased by 22% versus 44% in control group (P less than 0.05). Compared with control cells, cells treated with CDPC during anoxia maintained a significantly greater inotropic state. The effect is greatest if the cells are weak, as in series I. CDPC may be a useful component of the cardioplegic mixture during cardiopulmonary bypass and in the treatment of myocardial ischemia.

Animals↗

Intracellular distribution of enzymes of the cytidine diphosphate choline pathway in castor bean endosperm.

The occurrence and subcellular distribution of enzymes of the cytidine diphosphate choline pathway of lecithin synthesis have been examined. Choline kinase (EC 2.7.1.32) was completely soluble, while phosphorylcholine-cytidyl transferase (EC 2.7.7.15) and phosphorylcholine-glyceride transferase (EC 2.7.8.2) were associated with particulate fractions. Although components sedimenting at 10,000 to 100,000 x g contained both enzymes, phosphorylcholine-cytidyl transferase and particularly phosphorylcholine-glyceride transferase were present in the 10,000 x g pellet, which contained the major organelles, mitochondria, and glyoxysomes. When the crude homogenate was centrifuged on a sucrose density gradient, four major bands of particulate protein were recovered. A band at density 1.24 g/cm(3) contained the glyoxysomes and was devoid of phosphorylcholine-cytidyl transferase and phosphorylcholine-glyceride transferase activity. Enzyme activity was barely detectable in the mitochondria, at density 1.18 g/cm(2). Phosphorylcholine-glyceride transferase was found almost exclusively in a sharp band at density 1.12 g/cm(3), and phosphorylcholinecytidyl transferase was found in the uppermost band at density 1.08 g/cm(3). Thus, for the synthesis of lecithin in their membranes, the glyoxysomes and mitochondria depend on enzymes elsewhere in the cell; the final two steps in lecithin formation occur, apparently exclusively, in separate particulate cell components.

Carbon Isotopes↗

Cytidine diphosphate diglyceride analogs of antiretroviral dideoxynucleosides: evidence for release of dideoxynucleoside-monophosphates by phospholipid biosynthetic enzymes in rat liver subcellular fractions.

We recently synthesized phospholipid analogs with antiviral nucleosides in the polar headgroup and demonstrated their antiretroviral activity in vitro in human immunodeficiency virus-infected cells (Hostetler, K.Y., Stuhmiller, L.M., Lenting, H.B.M., van den Bosch, H. and Richman, D.D. (1990) J. Biol. Chem. 265, 6112-6117). Dideoxynucleoside analogs of cytidine diphosphate diglyceride (CDP-DG) represent one class of such phospholipid prodrugs from which the antiviral active principle may be released through established pathways of cellular phospholipid metabolism. We now demonstrate that the liponucleotides of dideoxycytidine, 3'-deoxythymidine and 3'-azido-3'-deoxythymidine (AZT, Zidovudine) can substitute to varying extents for CDP-DG in the biosynthesis of phosphatidylinositol, phosphatidylglycerol or diphosphatidylglycerol by rat liver subcellular fractions. In all three biosynthetic pathways dideoxycytidine diphosphate diglyceride was the most active donor of the phosphatidyl unit. The nearly stoichiometric formation of dideoxycytidine-5'-monophosphate during phosphatidylinositol biosynthesis supports the rationale that the antiretroviral liponucleotides may provide cells with a depot form from which the antiviral drug can be released in 5'-monophosphorylated form, thus bypassing the initial phosphorylation of free dideoxynucleosides.

Animals↗

Therapeutic effect of orally applied cytidine diphosphate choline in mild and severe degrees of normobaric and normocapnic degrees of hypoxia of rats.

Eighty Wistar rats were maintained under conditions of chronic hypoxic for a period of 5 months. After gradual adaptation to the reduced oxygen content of the inhaled air, animals were kept on the levels of 15, 12, 10 and 7 vol% O2 and their behaviour in an open field was observed. One group of 40 animals received CDP-choline (cytidine diphosphate choline, Somazina; CAS 1477-47-0) at a dose of 100 mg/kg body weight in their food. Hypoxia-induced behavioural deteriorations were partly mitigated by this substance. Therapeutic application of CDP-choline was more effective than prophylactic administration. The efficiency of CDP-choline decreased after prolonged application. Under conditions of extreme hypoxia CDP-choline exhibited a life prolonging effect.

Administration, Oral↗