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Gastrointestinal Tract as a Major Route of Pharmaceutical Administration
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
An antiporter (also called exchanger or cotransporter) is a cotransporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma membrane in opposite directions. In this type of indirect active transport, the driving ion (also usually Na+) diffuses through the pump in one direction and that transfer provides the energy for the active transport of another molecule in the opposite direction. An example of this type of pump is the H+/K+ ATPase which catalyzes the transport of H+ out of the gastric parietal cell (toward the lumen of the stomach) in exchange for a K+ ion which enters the cells (away from the lumen of the stomach) (Pak et al., 2013).
Therapeutic Nutrition
Published in W. John Diamond, The Clinical Practice of Complementary, Alternative, and Western Medicine, 2017
Phase III detoxification reaction. Recent studies have shown the activity of another detoxification reaction called “antiporter” activity. This antiporter activity is important in the first pass metabolism of pharmaceuticals and other xenobiotics. The antiporter is an energy-dependent efflux pump that pumps xenobiotics out of a cell, thereby decreasing the intracellular concentration of the drug or xenobiotic. Two genes encoding antiporter activity in regard to multiple drug resistance in cancer cell lines (MDR1) and in the liver (MDR2) have been defined.
Transport Kinetics
Published in John C. Matthews, Fundamentals of Receptor, Enzyme, and Transport Kinetics, 2017
Many active transport systems operate on an antiport or symport basis. Antiport transporters move a solute molecule from an area of low concentration across the membrane to an area of high concentration. This is accomplished by also transporting a different solute molecule across the membrane in the opposite direction from an area of high concentration to one of low concentration. The energy for moving the substance from low to high concentration is supplied by the substance that is moving from high to low concentration.
Modulations of ferroptosis in lung cancer therapy
Published in Expert Opinion on Therapeutic Targets, 2022
Robert Walters, Shaker A. Mousa
Cells use the system Xc− (glutamate – cystine) antiporter to export glutamate and import cystine across the plasma membrane in a 1:1 fashion [9]. Inhibition of this antiporter can increase oxidative stress and mediate the toxicity of glutamate. Once cystine is in the cell, it will be catalyzed to cysteine and further catalyzed to GSH. GSH serves as an intracellular antioxidant buffer and maintains redox balance in the presence of GPX4. Ferroptosis is induced due to depletion of this antioxidant buffer, causing increased oxidative injury. GSH depletion was shown to induce ferroptosis, autophagy, and SIPS [10]. There are three major upstream factors contributing to GSH depletion, including glutamine decomposition, cysteine deprivation, and high extracellular glutamate [11].
Efflux proteins at the blood–brain barrier: review and bioinformatics analysis
Published in Xenobiotica, 2018
Massoud Saidijam, Fatemeh Karimi Dermani, Sareh Sohrabi, Simon G. Patching
SLC transporters mediate the transport (uptake and/or export) of a wide range of substrates (e.g. ions, inorganic and organic metabolites, peptides, drugs, xenobiotics) across biological membranes using diverse mechanisms (e.g. passive transport, facilitated transport, symport, antiport). Around 400 human SLC transporter genes have been identified that include around 50 different families based on sequence similarities (He et al., 2009; Hediger et al., 2013; Schlessinger et al., 2013a,b). Because SLC transporters have roles in many physiological processes and diseases and can be used for the cell- and tissue-specific uptake of drugs, they are emerging as important therapeutic targets that justifies further intensive and systematic research into their structure, function, molecular mechanisms and interactions with substrates (César-Razquin et al., 2015; Lin et al., 2015; Rask-Andersen et al., 2013). A number of SLC transporters with a function (or possible function) of active efflux at the blood–brain barrier have been identified (Kusuhara & Sugiyama, 2005), which to-date include members of the organic anion transporting polypeptide (OATP), organic anion transporter (OAT), excitatory amino acid transporter (EAAT), plasma membrane monoamine transporter (PMAT) and multidrug and toxic compound extrusion (MATE) families.
Rapamycin mitigates erythrocyte membrane transport functions and oxidative stress during aging in rats
Published in Archives of Physiology and Biochemistry, 2018
Abhishek Kumar Singh, Sandeep Singh, Geetika Garg, Syed Ibrahim Rizvi
The Na+/H+ exchanger (antiport) is an N-methyl-N-isobutyl amiloride sensitive and electroneutral ion exchange system present on the membrane of nearly all the mammalian cells that regulate the intracellular volume and pH of the cytoplasm (Asha Devi et al. 2009). The maintenance of regulated intracellular pH is necessary and critical for several physiological functions that provide suitable acid–base balanced microenvironment for the appropriate functioning of proteins/enzymes, ion channels and other biological functions (Pandey and Rizvi 2014). Our study demonstrates a significantly increased NHE activity in erythrocyte membrane of aged rats as compared to young rats. The treatment of rapamycin reversed the impaired activity of NHE in old-aged rats by decreasing the level of NHE in erythrocyte membrane. The Ser/Thr kinases of cytosolic domain of NHE1 have been reported to interact with ezrin/radixin/moesin proteins and phosphatidylinositol 4,5-bisphosphate to form a signalling complex that further phosphorylates and activates Akt to keep the cells away from apoptotic stress. In contrary, NHE1 also induces the onset of apoptotic cell death under the strong apoptotic stimuli (Schelling and Abu Jawdeh 2008). Thus, our data suggest that the NHE may act as a potential target for intervention to assess the therapeutic potential of compounds against oxidative stress.