Search results for "Organic anion"
showing 10 items of 33 documents
The inhibitory neural circuitry as target of antiepileptic drugs.
2001
Impairments and defects in the inhibitory neurotransmission in the CNS can contribute to various seizure disorders, i.e., gamma-aminobutyric acid (GABA) and glycine as the main inhibitory neurotransmitters in the brain play a crucial role in some forms of epilepsy. Recent advances in deciphering the molecular basis of the GABAergic and glycinergic systems has been achieved by means of cloning techniques and gene targeting strategies in animals, contributing to the understanding of drug action. As well, several anticonvulsive substances emerged which target key molecules of the inhibitory systems. Employment of recombinant expression systems, including, but not restricted to the inhibitory c…
Effects of GABA-transporter (GAT) inhibitors on rat behaviour in open-field and elevated plus-maze.
1999
The behavioural consequences of inhibition of gamma-aminobutyric acid (GABA) uptake were studied. Two GABA uptake inhibitors, tiagabine and SKF 89976-A, were administered to rats, and behaviour was analysed 30 min later in a standard open field, an enriched open field, and an elevated plus-maze. Eight groups of animals received either saline (0.9%), tiagabine, or SKF 89976-A. At a dose of 18.5 mg/kg, tiagabine, an established antiseizure drug, impaired motor coordination, enhanced exploratory activity and reduced anxiety related behaviour. SKF 89976-A exhibited minimal effects over the dose range tested. These results indicate that inhibition of GABA uptake might be a pharmacological strate…
Genotype and Allele Frequencies of Drug-Metabolizing Enzymes and Drug Transporter Genes Affecting Immunosuppressants in the Spanish White Population
2013
Interpatient variability in drug response can be widely explained by genetically determined differences in metabolizing enzymes, drug transporters, and drug targets, leading to different pharmacokinetic and/or pharmacodynamic behaviors of drugs. Genetic variations affect or do not affect drug responses depending on their influence on protein activity and the relevance of such proteins in the pathway of the drug. Also, the frequency of such genetic variations differs among populations, so the clinical relevance of a specific variation is not the same in all of them. In this study, a panel of 33 single nucleotide polymorphisms in 14 different genes (ABCB1, ABCC2, ABCG2, CYP2B6, CYP2C19, CYP2C…
Bis(glycylglycinium) oxalate at 100 K.
2003
The structure of the title compound, 2C(4)H(9)N(2)O(3)(+).C(2)O(4)(2-), which has been determined by X-ray diffraction, contains discrete glycylglycine (HGly-Gly)(+) cations in general positions and oxalate anions which lie across centres of inversion. Although the geometry of the (HGly-Gly)(+) cation is not significantly different compared with other structures containing this residue, a few changes in conformation are observed which indicate the presence of molecular interactions. The molecular network in the crystal consists of one nearly linear O-H...O, five N-H...O and two weak C-H.O hydrogen bonds.
Both cholestatic and steatotic drugs trigger extensive alterations in the mRNA level of biliary transporters in rat hepatocytes: Application to devel…
2016
Disruption of the vectorial bile acid transport in the liver is a key feature of cholestatic drugs, although many causal and mechanistic aspects are still unknown. The aim of the present study was to explore if cholestatic drugs can repress or induce the expression of hepatic transporters. To this end, sandwich-cultured rat hepatocytes were treated with cholestatic and non-cholestatic (steatotic, non-hepatotoxic, etc.) drugs and the mRNA expression of 10 uptake and efflux biliary transporters was measured. Results evidenced that all cholestatic drugs cause extensive alterations in the mRNA expression of most biliary transporters. Surprisingly, nearly all steatotic drugs also affected the ex…
Anti-hyperuricemic and nephroprotective effects of extracts from Chaenomeles sinensis (Thouin) Koehne in hyperuricemic mice
2018
Clinically, Chaenomeles sinensis (Thouin) Koehne (C. sinensis) has been used to treat hyperuricemia and gout. However, the exact mechanism of action is still unknown. In the present study, the ethyl acetate fraction of C. sinensis fruit extract (CSF-E) was separated. Potassium oxonate (PO)-induced hyperuricemic mice and normal mice were administered with CSF-E at 60, 120 and 180 mg kg-1, respectively for 7 days. Serum uric acid, creatinine and BUN levels, liver oxidative damage, and serum and hepatic XOD activities were primarily measured using assay kits. The evaluation of its nephroprotective effects was carried out by renal histopathological analysis. Simultaneously, renal protein levels…
Behavioral Effects of GABAA Receptor Stimulation and GABA-Transporter Inhibition
2000
Abstract The present analysis addressed behavioral changes after treatment with 4.5 mg/kg or 18.5 mg/kg of the GABA-uptake inhibitor tiagabine combined with either the benzodiazepine diazepam (1.5 mg/kg) or the imidazopyridine zolpidem (0.05 mg/kg), the latter two acting differentially on GABA A receptor subtypes. The study included 97 male PVG/OIaHsd rats. A standard open field, an enriched open field, and an elevated plus-maze was used to study rat behavior. Treatment with the low dose of tiagabine alone induced no specific behavioral effects, whereas the high dose had an anxiolytic-like potential. Furthermore, diazepam but not zolpidem displayed anxiolytic-like effects. Combination of ea…
A conserved role for the mitochondrial citrate transporter Sea/SLC25A1 in the maintenance of chromosome integrity.
2009
Histone acetylation plays essential roles in cell cycle progression, DNA repair, gene expression and silencing. Although the knowledge regarding the roles of acetylation of histone lysine residues is rapidly growing, very little is known about the biochemical pathways providing the nucleus with metabolites necessary for physiological chromatin acetylation. Here, we show that mutations in the scheggia (sea)-encoded Sea protein, the Drosophila ortholog of the human mitochondrial citrate carrier Solute carrier 25 A1 (SLC25A1), impair citrate transport from mitochondria to the cytosol. Interestingly, inhibition of sea expression results in extensive chromosome breakage in mitotic cells and indu…
Tiagabine, a gamma-amino-butyric acid transporter inhibitor impairs spatial learning of rats in the Morris water-maze.
2002
Abstract γ-Amino-butyric acid (GABA) is cleaved from the synaptic cleft by uptake via specific transporters. Inhibition of such transporters increases the effectiveness of physiologically released GABA. Increased GABAergic neurotransmission has an impact on learning and memory. Therefore, effects of tiagabine, a GABA-transporter inhibitor, were investigated on spatial orientation in the Morris water-maze. Rats were given four training trials per day for 4 days and a probe trial without platform on the 5th day. Compared to saline treated rats, rats treated daily with 20 mg/kg tiagabine showed impaired learning during the acquisition trials. Retrieval was impaired in rats treated only at the …
Effects of typical inducers on olfactory xenobiotic-metabolizing enzyme, transporter, and transcription factor expression in rats.
2010
International audience; Several xenobiotic-metabolizing enzymes (XMEs) have been identified in the olfactory mucosa (OM) of mammals. However, the molecular mechanisms underlying the regulation of these enzymes have been little explored. In particular, information on the expression of the transcriptional factors in this tissue is quite limited. The aim of the present study was to examine the impact of five typical inducers, Aroclor 1254, 3-methylcholanthrene, dexamethasone, phenobarbital, and ethoxyquin, on the activities and mRNA expression of several XMEs in the OM and in the liver of rats. We also evaluated the effects of these treatments on the mRNA expression of transcription factors an…