Uptake Transporters of the Human OATP Family

2010 ◽  
pp. 1-28 ◽  
Author(s):  
Jörg König
Keyword(s):  
Uptake Transporters

Expression and localization of hepatocellular uptake transporters, export pumps, and radixin in primary biliary cirrhosis

2004 ◽  
Vol 42 (01) ◽  
Author(s):  
AT Nies ◽  
H Kojima ◽  
J König ◽  
W Hagmann ◽  
H Spring ◽  
...  
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Biliary Cirrhosis ◽  
Uptake Transporters

The Effects of Drug Metabolizing Enzyme Inhibitors on Hepatic Efflux and Uptake Transporters

2018 ◽  
Vol 11 (2) ◽  
Author(s):  
Jonathan Cheong ◽  
Jason S. Halladay ◽  
Emile Plise ◽  
Jasleen K. Sodhi ◽  
Laurent Salphati
Keyword(s):  
Enzyme Inhibitors ◽  
Drug Metabolizing Enzyme ◽  
Metabolizing Enzyme ◽  
Uptake Transporters

scholarly journals Expression and Function of Organic Anion Transporting Polypeptides in the Human Brain: Physiological and Pharmacological Implications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 834
Author(s):  
Anima M. Schäfer ◽  
Henriette E. Meyer zu Schwabedissen ◽  
Markus Grube
Keyword(s):  
Organic Anion ◽  
Physiological Role ◽  
Point Of View ◽  
Efflux Transporters ◽  
Organic Anion Transporting Polypeptides ◽  
Current State ◽  
P Glycoprotein ◽  
The Central Nervous System ◽  
And Function ◽  
Uptake Transporters

The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood–brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters like P-Glycoprotein are involved in the integrity of this barrier. In addition to these, however, uptake transporters have also been found to selectively uptake certain compounds into the CNS. These transporters are localized in the BBB as well as in neurons or in the choroid plexus. Among them, from a pharmacological point of view, representatives of the organic anion transporting polypeptides (OATPs) are of particular interest, as they mediate the cellular entry of a variety of different pharmaceutical compounds. Thus, OATPs in the BBB potentially offer the possibility of CNS targeting approaches. For these purposes, a profound understanding of the expression and localization of these transporters is crucial. This review therefore summarizes the current state of knowledge of the expression and localization of OATPs in the CNS, gives an overview of their possible physiological role, and outlines their possible pharmacological relevance using selected examples.

scholarly journals Axonal Modulation of Striatal Dopamine Release by Local γ-Aminobutyric Acid (GABA) Signalling

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 709
Author(s):  
Bradley M. Roberts ◽  
Emanuel F. Lopes ◽  
Stephanie J. Cragg
Keyword(s):  
Gabab Receptors ◽  
Striatal Dopamine ◽  
Aminobutyric Acid ◽  
Gaba Uptake ◽  
Short Term Plasticity ◽  
Psychomotor Disorders ◽  
Gabaa And Gabab Receptors ◽  
Uptake Transporters ◽  
Gabaergic Modulation ◽  
Da Release

Striatal dopamine (DA) release is critical for motivated actions and reinforcement learning, and is locally influenced at the level of DA axons by other striatal neurotransmitters. Here, we review a wealth of historical and more recently refined evidence indicating that DA output is inhibited by striatal γ-aminobutyric acid (GABA) acting via GABAA and GABAB receptors. We review evidence supporting the localisation of GABAA and GABAB receptors to DA axons, as well as the identity of the striatal sources of GABA that likely contribute to GABAergic modulation of DA release. We discuss emerging data outlining the mechanisms through which GABAA and GABAB receptors inhibit the amplitude as well as modulate the short-term plasticity of DA release. Furthermore, we highlight recent data showing that DA release is governed by plasma membrane GABA uptake transporters on striatal astrocytes, which determine ambient striatal GABA tone and, by extension, the tonic inhibition of DA release. Finally, we discuss how the regulation of striatal GABA-DA interactions represents an axis for dysfunction in psychomotor disorders associated with dysregulated DA signalling, including Parkinson’s disease, and could be a novel therapeutic target for drugs to modify striatal DA output.

scholarly journals Biphasic unbinding of a metalloregulator from DNA for transcription (de)repression in Live Bacteria

2020 ◽  
Vol 48 (5) ◽  
pp. 2199-2208
Author(s):  
Won Jung ◽  
Kushal Sengupta ◽  
Brian M Wendel ◽  
John D Helmann ◽  
Peng Chen
Keyword(s):  
Single Molecule ◽  
Protein Concentration ◽  
Consensus Sequence ◽  
Salt Bridges ◽  
Ternary Complex Formation ◽  
Escherichia Coli Cells ◽  
Live Bacteria ◽  
Zinc Sensing ◽  
Conventional Models ◽  
Uptake Transporters

Abstract Microorganisms use zinc-sensing regulators to alter gene expression in response to changes in the availability of zinc, an essential micronutrient. Under zinc-replete conditions, the Fur-family metalloregulator Zur binds to DNA tightly in its metallated repressor form to Zur box operator sites, repressing the transcription of zinc uptake transporters. Derepression comes from unbinding of the regulator, which, under zinc-starvation conditions, exists in its metal-deficient non-repressor forms having no significant affinity with Zur box. While the mechanism of transcription repression by Zur is well-studied, little is known on how derepression by Zur could be facilitated. Using single-molecule/single-cell measurements, we find that in live Escherichia coli cells, Zur's unbinding rate from DNA is sensitive to Zur protein concentration in a first-of-its-kind biphasic manner, initially impeded and then facilitated with increasing Zur concentration. These results challenge conventional models of protein unbinding being unimolecular processes and independent of protein concentration. The facilitated unbinding component likely occurs via a ternary complex formation mechanism. The impeded unbinding component likely results from Zur oligomerization on chromosome involving inter-protein salt-bridges. Unexpectedly, a non-repressor form of Zur is found to bind chromosome tightly, likely at non-consensus sequence sites. These unusual behaviors could provide functional advantages in Zur's facile switching between repression and derepression.

scholarly journals Regulation of Sulfate Uptake and Assimilation in Barley (Hordeum vulgare) as Affected by Rhizospheric and Atmospheric Sulfur Nutrition

Plants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1283
Author(s):  
Ties Ausma ◽  
Luit J. De Kok
Keyword(s):  
Hordeum Vulgare ◽  
Biomass Production ◽  
Signal Transduction Pathway ◽  
Mineral Nutrient ◽  
Sulfur Source ◽  
Sulfate Uptake ◽  
Protein Levels ◽  
Amino Acid Contents ◽  
Uptake Transporters ◽  
Expression And Activity

To study the regulation of sulfate metabolism in barley (Hordeum vulgare), seedlings were exposed to atmospheric hydrogen sulfide (H2S) in the presence and absence of a sulfate supply. Sulfate deprivation reduced shoot and root biomass production by 60% and 70%, respectively, and it affected the plant’s mineral nutrient composition. It resulted in a 5.7- and 2.9-fold increased shoot and root molybdenum content, respectively, and a decreased content of several other mineral nutrients. Particularly, it decreased shoot and root total sulfur contents by 60% and 70%, respectively. These decreases could be ascribed to decreased sulfate contents. Sulfate deficiency was additionally characterized by significantly lowered cysteine, glutathione and soluble protein levels, enhanced dry matter, nitrate and free amino acid contents, an increased APS reductase (APR) activity and an increased expression and activity of the root sulfate uptake transporters. When sulfate-deprived barley was exposed to 0.6 µL L−1 atmospheric H2S, the decrease in biomass production and the development of other sulfur deficiency symptoms were alleviated. Clearly, barley could use H2S, absorbed by the foliage, as a sulfur source for growth. H2S fumigation of both sulfate-deprived and sulfate-sufficient plants downregulated APR activity as well as the expression and activity of the sulfate uptake transporters. Evidently, barley switched from rhizospheric sulfate to atmospheric H2S as sulfur source. Though this indicates that sulfate utilization in barley is controlled by signals originating in the shoot, the signal transduction pathway involved in the shoot-to-root regulation must be further elucidated.

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