Search results for "Membrane transport protein"
showing 10 items of 159 documents
Characterisation of serotonin transport mechanisms in rainbow trout peripheral blood lymphocytes: role in PHA-induced lymphoproliferation
1999
Abstract AbstractIn this study we investigated the serotonin transport mechanisms in rainbow trout (Oncorhynchus mykiss) peripheral blood lymphocytes We have observed that the transport of serotonin is a membrane transport process that have the properties of a secondary active transport system The binding isotherm of [3H]-paroxetine a serotonin transport blocker demonstrated a high-affinity binding site with a positive type of cooperativity Hill coefficient being higher than unity Known specific inhibitors of the mammalian serotonin transporter significantly inhibited the uptake process in fish lymphocytes In order to demonstrate the physiological relevance of the serotonin transporter in T…
Computer simulations for bioequivalence trials: Selection of analyte in BCS class II and IV drugs with first-pass metabolism, two metabolic pathways …
2018
A semi-physiological two compartment pharmacokinetic model with two active metabolites (primary (PM) and secondary metabolites (SM)) with saturable and non-saturable pre-systemic efflux transporter, intestinal and hepatic metabolism has been developed. The aim of this work is to explore in several scenarios which analyte (parent drug or any of the metabolites) is the most sensitive to changes in drug product performance (i.e. differences in in vivo dissolution) and to make recommendations based on the simulations outcome. A total of 128 scenarios (2 Biopharmaceutics Classification System (BCS) drug types, 2 levels of KM Pgp, in 4 metabolic scenarios at 2 dose levels in 4 quality levels of t…
The Low-Affinity ATP Binding Site of the Escherichia coli SecA Dimer Is Localized at the Subunit Interface
1997
The homodimeric SecA protein is the ATP-dependent force generator in the Escherichia coli precursor protein translocation cascade. SecA contains two essential nucleotide binding sites (NBSs), i.e., NBS1 and NBS2 that hind ATP with high and low affinity, respectively. The photoactivatable bifunctional cross-linking agent 3'-arylazido-8-azidoadenosine 5'-triphosphate (diN(3)ATP) was used to investigate the spatial arrangement of the nucleotide binding sites of SecA, DiN(3)ATP is an authentic ATP analogue as it supports SecA-dependent precursor protein translocation and translocation ATPase, UV-induced photo-cross-linking of the diN(3)ATP-bound SecA results in the formation of stable dimeric s…
Functional characterization of ORCTL2--an organic cation transporter expressed in the renal proximal tubules.
1998
AbstractChromosome 11p15.5 harbors a gene or genes involved in Beckwith-Wiedemann syndrome that confer(s) susceptibility to Wilms' tumor, rhabdomyosarcoma, and hepatoblastoma. We have previously identified a transcript at 11p15.5 which encodes a putative membrane transport protein, designated organic cation transporter-like 2 (ORCTL2), that shares homology with tetracycline resistance proteins and bacterial multidrug resistance proteins. In this report, we have investigated the transport properties of ORCTL2 and show that this protein can confer resistance to chloroquine and quinidine when overexpressed in bacteria. Immunohistochemistry analyses performed with anti-ORCTL2 polyc.onal antibod…
Involvement of the Pseudomonas aeruginosa MexAB–OprM efflux pump in the secretion of the metallophore pseudopaline
2020
ABSTRACTThe ability for all organisms to acquire metals from their environment is essential for life. To overcome the metal restriction imposed by the host’s nutritional immunity, bacterial pathogens exploits the use of small high metal affinity molecules called metallophores. Metallophores are first synthetized in the cytoplasm, then secreted into the medium where they sequester the metal. The metal-metallophore complex is then imported into the bacterium following binding to dedicated cell surface receptors. Recently, a new family of metallophores has been discovered in pathogenic bacteria called staphylopine in Staphylococcus aureus and pseudopaline in Pseudomonas aeruginosa. Here, we ar…
The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.
2006
Contains fulltext : 35205.pdf (Publisher’s version ) (Closed access) Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, nor…
Association study of 44 candidate genes with depressive and anxiety symptoms in post-partum women.
2009
The post-partum period is a time of extreme vulnerability for a whole spectrum of psychiatric disorders. Delivery may be considered an important risk factor in genetically susceptible women. Five hundred and eight SNPs in 44 genes at candidate pathways putatively related to mood changes after delivery were genotyped in a multicenter cohort of 1804 women from Spain. Participants completed two scales at 2-3 days, 8 weeks, and 32 weeks post-partum, the Edinburgh Post-partum Depression Scale (EPDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Those women who scored 9 or more on EPDS were evaluated for major depression using the Diagnostic Interview for Genetics Studies (DIGS) adapt…
Down-regulation of OPA1 alters mouse mitochondrial morphology, PTP function, and cardiac adaptation to pressure overload
2012
AIMS: The optic atrophy 1 (OPA1) protein is an essential protein involved in the fusion of the mitochondrial inner membrane. Despite its high level of expression, the role of OPA1 in the heart is largely unknown. We investigated the role of this protein in Opa1(+/-) mice, having a 50% reduction in OPA1 protein expression in cardiac tissue. METHODS AND RESULTS: In mutant mice, cardiac function assessed by echocardiography was not significantly different from that of the Opa1(+/+). Electron and fluorescence microscopy revealed altered morphology of the Opa1(+/-) mice mitochondrial network; unexpectedly, mitochondria were larger with the presence of clusters of fused mitochondria and altered c…
Kinetic modelling of passive transport and active efflux of a fluoroquinolone across Caco-2 cells using a compartmental approach in NONMEM.
2005
The purpose was to develop a general mathematical model for estimating passive permeability and efflux transport parameters from in vitro cell culture experiments. The procedure is applicable for linear and non-linear transport of drug with time,10 or10% of drug transport, negligible or relevant back flow, and would allow the adequate correction in the case of relevant mass balance problems. A compartmental kinetic approach was used and the transport barriers were described quantitatively in terms of apical and basolateral clearances. The method can be applied when sink conditions are not achieved and it allows the evaluation of the location of the transporter and its binding site. In this …
Gray Matter NG2 Cells Display Multiple Ca2+-Signaling Pathways and Highly Motile Processes
2011
NG2 cells, the fourth type of glia in the mammalian CNS, receive synaptic input from neurons. The function of this innervation is unknown yet. Postsynaptic changes in intracellular Ca(2+)-concentration ([Ca(2+)](i)) might be a possible consequence. We employed transgenic mice with fluorescently labeled NG2 cells to address this issue. To identify Ca(2+)-signaling pathways we combined patch-clamp recordings, Ca(2+)-imaging, mRNA-transcript analysis and focal pressure-application of various substances to identified NG2-cells in acute hippocampal slices. We show that activation of voltage-gated Ca(2+)-channels, Ca(2+)-permeable AMPA-receptors, and group I metabotropic glutamate-receptors provo…