Pyrimidines and CNS regulation

Connolly, G.P.; Simmonds, H. Anne; Dulay, John A.

doi:10.1016/0165-6147(96)20001-x

Cited by 27 publications

(14 citation statements)

References 7 publications

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“…There is an increasing awareness that pyrimidines play an important role in the regulation of the central nervous system and that metabolic changes affecting the levels of pyrimidines may lead to abnormal neurological activity (Connolly et al 1996). Indeed, the anti-convulsant effects of uridine in animals with experimentally induced seizures indicate that pyrimidine compounds may play an important role in regulating the activity of the nervous system (Roberts 1973).…”

Section: Pyrimidine Basesmentioning

confidence: 99%

Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency

Kuilenburg

Vreken

Abeling³

et al. 1999

Hum Genet

256

170

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Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disease characterised by thymine-uraciluria in homozygous deficient patients and has been associated with a variable clinical phenotype. In order to understand the genetic and phenotypic basis for DPD deficiency, we have reviewed 17 families presenting 22 patients with complete deficiency of DPD. In this group of patients, 7 different mutations have been identified, including 2 deletions [295-298delTCAT, 1897delC], 1 splice-site mutation [IVS14+1G>A)] and 4 missense mutations (85T>C, 703C>T, 2658G>A, 2983G>T). Analysis of the prevalence of the various mutations among DPD patients has shown that the G-->A point mutation in the invariant splice donor site is by far the most common (52%), whereas the other six mutations are less frequently observed. A large phenotypic variability has been observed, with convulsive disorders, motor retardation and mental retardation being the most abundant manifestations. A clear correlation between the genotype and phenotype has not been established. An altered beta-alanine, uracil and thymine homeostasis might underlie the various clinical abnormalities encountered in patients with DPD deficiency.

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Section: Pyrimidine Basesmentioning

confidence: 99%

Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency

Kuilenburg

Vreken

Abeling³

et al. 1999

Hum Genet

256

170

View full text Add to dashboard Cite

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“…It is believed that the mammalian brain has limited capacity for the de novo synthesis of purines and pyrimidines; thus, this organ is reliant upon a supply of circulating purines and pyrimidines [1][2][3][4], which originate principally from the liver and kidney [3,5,6]. In addition to the uptake from blood, nucleosides are also produced in the brain by two pathways; extracellularly, by the action of ecto-5 0 -nucleotidases on nucleoside phosphates (like ATP) [7] and, intracellularly, through the action of soluble 5 0 -nucleotidases; the latter showing much higher capacity than ecto-5 0 -nucleotidases [8].…”

Section: Introductionmentioning

confidence: 99%

Blood–Brain Barrier Efflux Transport of Pyrimidine Nucleosides and Nucleobases in the Rat

et al. 2008

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The brain efflux index (BEI), a measurement of blood-brain barrier (BBB) efflux transport, was estimated at 15 s, 30 s, 1 min, 3 min and 10 min after intracerebral injection of [14C]pyrimidines. An initial steep increase of the BEI values over time was observed for [14]uracil and [14C]thymine, followed by a more moderate increase after 1 min. For the corresponding nucleosides, [14C]uridine and [14C]thymidine, the increase of BEI values over time was less steep and linear between 30 s and 3 min. The apparent BBB efflux clearances for [14C]uridine, [14C]thymidine, [14C]uracil and [14C]thymine were (microl/min/g): 95.2 +/- 12.1, 125.3 +/- 18.4, 290.4 +/- 28 and 358.5 +/- 32.5, respectively, which is at least several folds higher than the predicted BBB influx clearances of uridine, uracil and thymidine. Quick depletion of brain parenchyma from brain microvasculature has revealed that [14C] radioactivity accumulated in brain microvessels after injection of nucleosides [14C]thymidine and [14C]uridine, but that was not observed when nucleobases, [14C]thymine and [14C]uracil, were injected. Reverse transcriptase-PCR revealed that the rat brain and liver (positive control) express dihydropyrimidine dehydrogenase, a key enzyme in pyrimidine nucleobase catabolism. Two bands representing spliced variants have been detected with the relative density of the bands (expressed relative to the density of glyceraldehyde3-phosphate dehydrogenase bands, mean +/- SEM from 3 separate samples) 0.16 +/- 0.06 and 0.04 +/- 0.01 (brain) and 0.49 +/- 0.1 and 0.07 +/- 0.01 (liver). Overall, these results indicate that the net direction of pyrimidine BBB transport is the efflux transport; rapid BBB efflux transport and metabolic breakdown of pyrimidine nucleobases appear to be important for brain homeostasis.

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“…8-azapurines possess antipurine, antifungal, antiviral and anticancer properties [4]. Hence methods for determining purine and pyrimidine bases that are quick, inexpensive and accurate are needed in many areas of research such as clinical diagnosis and in pharmacological studies [5,6].…”

Section: Introductionmentioning

confidence: 99%

Enhanced separation of purine and pyrimidine bases using carboxylic multiwalled carbon nanotubes as additive in capillary zone electrophoresis

et al. 2006

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This paper describes the enhanced separation of adenine (A), hypoxanthine (HX), 8-azaadenine (8-AA), thymine (T), cytosine (C), uracil (U) and guanine (G) by CZE dispersing carboxylic multiwalled carbon nanotubes (c-MWNTs) into the running buffer. The effect of important factors such as c-MWNT nanoparticle concentration, the acidity and concentration of running buffer, and separation voltage were investigated to acquire the optimum conditions. The seven purine and pyrimidine bases could be well separated within 16 min in a 35 cm effective length fused-silica capillary at a separation voltage of +8.0 kV in a 23 mM tetraborate buffer (pH 9.2) containing 8.0 x 10(-5) g/mL c-MWNTs. Under the optimal conditions, the linear ranges were of 2-250 microg/mL for A (R2 = 0.995), 3-200 microg/mL for U (R2 = 0.990) and G (R2 = 0.992), 3-250 microg/mL for T (R2 = 0.998), 2-200 microg/mL for C (R2 = 0.985) and 4-200 microg/mL for HX (R2 = 0.988) and 8-AA (R2 = 0.990). The detection limits were 0.9 microg/mL for A (S/N = 3), 2.4 microg/mL for U, 2.0 microg/mL for T, 1.5 microg/mL for C, 2.5 microg/mL for G and 3.0 microg/mL for HX and 8-AA. The proposed method was successfully applied for determining five purine and pyrimidine bases in yeast RNA.

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Pyrimidines and CNS regulation

Cited by 27 publications

References 7 publications

Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency

Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency

Blood–Brain Barrier Efflux Transport of Pyrimidine Nucleosides and Nucleobases in the Rat

Enhanced separation of purine and pyrimidine bases using carboxylic multiwalled carbon nanotubes as additive in capillary zone electrophoresis

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