Role of Transport in Chemically-Induced Nephrotoxicity *
Robin S. Goldstein in Mechanisms of Injury in Renal Disease and Toxicity, 2020
Organic cations (e.g., tetraethylammonium [TEA]) are transported rapidly by proximal tubular cells. The anatomical localization of this transport is similar to that for PAH, although not as well characterized. McKinney (1982) demonstrated in the rabbit that the S2 and S3 cells are most active for cation transport. It is likely that species differences also exist with respect to localization of cation transport, although detailed studies have not been forthcoming. As noted above, organic cation and anion transport systems are completely separate. Other cations such as N-methylnicotinamide or quinine will inhibit cation transport, but not alter anion transport. Phenoxybenzamine produces an irreversible inhibition of cation transport, apparently by binding covalently to the transporter. An irreversible inhibitor of PAH transport has not been found. DNP also inhibits the transport of TEA, but this effect is related totally to the inhibition of energy metabolism. Cyanine 863 also blocks selectively organic cation transport competitively at low doses, and, perhaps, noncompetitively at high doses.
Cell Biology
John D Firth, Professor Ian Gilmore in MRCP Part 1 Self-Assessment, 2017
Na/K-ATPase transporters are found in all living cells in the body. They are comprised of alpha and beta subunits, the alpha subunit containing regions that coordinate cation transport and regions that bind and hydrolyse ATP, releasing energy to drive the transport of three sodium ions out of the cell for every two potassium ions imported. Action of the pump, which is inhibited by digoxin, maintains the cell’s resting membrane potential.
Pharmacology
Bhaskar Punukollu, Michael Phelan, Anish Unadkat in MRCPsych Part 1 In a Box, 2019
Mechanism of action: Not fully understood. Has effects on cation transport increasing Na/K ATPase pump activity. Also increases generation and release of 5HT. It increases transmission at 5HT1a and decreases transmission at 5HT2 receptors. It enhances noradrenaline synaptic uptake as well as platelet 5HT uptake. It also increases acetylcholine levels.
‘Trojan-Horse’ stress-granule formation mediated by manganese oxide nanoparticles
Published in Nanotoxicology, 2020
Nina B. Illarionova, Ksenia N. Morozova, Dmitry V. Petrovskii, Marina B. Sharapova, Alexander V. Romashchenko, Sergey Y. Troitskii, Elena Kiseleva, Yuri M. Moshkin, Mikhail P. Moshkin
Comparison of Mn2+- and Mn3O4 NPs-mediated SGs formation has revealed a faster turnover of cation induced SGs assembly and disassembly. Mn2+ cations are transported into the cell by divalent metal ion transporter (DMT1) and/or through calcium ion channels (Lucaciu et al. 1997; Garrick et al. 2003), and could readily reach mitochondria. Instead, NPs are primarily taken up by endocytosis (Oh and Park, 2014) and, expectedly, more time is needed for them to release cations by partial dissolution. However, while a bulk of Mn2+ induced SGs was disassembled already after 15 min of incubation, SGs formed by Mn3O4 NPs continued to accumulate and persisted for hours. Along with prolonged metabolic dysfunction, this could be a prerequisite for chronic cell stress and might be an associated factor in the development of neurodegenerative disorders (Vanderweyde et al. 2013; Chen and Liu 2017; Dobra et al. 2018; Reineke and Neilson 2019).
The Silk Protein Sericin Promotes Viability of ARPE-19 and Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelial Cells in vitro
Published in Current Eye Research, 2021
Ayyad Zartasht Khan, Tor Paaske Utheim, Morten Carstens Moe, Hans Christian D. Aass, Dipak Sapkota, Evan Michael Vallenari, Jon Roger Eidet
Closely related to pH are the dynamics of sodium, potassium, calcium, and chloride. Sericin-treated cultures showed lower levels of extracellular potassium and calcium, while extracellular levels of sodium and chloride were increased in comparison to untreated cultures. This pattern fits well with an increased activity of Na+/K+-ATPase, the chief ion transporter in RPE. The Na+/K+-ATPase shifts potassium intracellularly and transports sodium out of the cell, generating a sodium gradient that is used by the Na+/2Cl−/K+-co-transporter to accumulate chloride intracellularly.4 Importantly, Na+/K+-ATPase-activity was not assessed in the current experiments, and statements concerning this pump must be considered speculations only.
An overview of carbonic anhydrases and membrane channels of synoviocytes in inflamed joints
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Currently, experimental evidence for the involvement of CAs and FLS membrane channels in RA is limited. The physiological and pathological roles of ion channels and transporters in dynamic FLS migration have not yet been studied in detail. Here, we have summarised the studies on membrane channels and regulatory enzymes of RA-FLS with an aim to understand their migrated state. However, many questions regarding RA-FLS still need to be clarified. What are the exact molecular mechanisms by which ion transporter affects the FLS migration apparatus? What are the exact components of synovial fluid that mediate the FLS dynamics? What are the components affecting the differential expression of CAs and membrane channels in FLS? What is the combined mechanism of CAs as regulatory enzymes? Several membrane channels and transporters show tissue-specific expression. Thus, unravelling the mechanisms by which ion channels and transporters are positioned in and modulate the migration of activated FLS will be a rewarding pursuit for the coming years. The motivation of channel physiologists is also needed to develop potential therapeutics to counter the critical pathophysiological involvement of FLS migration in joints in RA.
Related Knowledge Centers
- Atp Synthase
- Facilitated Diffusion
- Transmembrane Protein
- Ion Channel
- Biological Membrane
- Adenosine Triphosphate
- Redox
- Passive Transport
- Ion Transporter Superfamily
- Membrane Transport Protein