TY - JOUR. T1 - Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal renal tubules and hOAT1 expressed in human kidney epithelial cells. AU - Sauvant, C.. AU - Hesse, D.. AU - Holzinger, H.. AU - Evans, K. K.. AU - Dantzler, William H. AU - Gekle, M.. PY - 2004/4. Y1 - 2004/4. N2 - We recently showed that, in a proximal tubule cell line (opossum kidney cells), epithelial growth factor (EGF) stimulates basolateral organic anion transport (OAT) via ERK1/2, arachidonic acid, phospholipase A2, and generation of prostaglandins. PGE2 binds the prostanoid receptor and, thus, activates adenylate cyclase and PKA, which stimulate basolateral organic anion uptake. In the present study, we investigated whether this regulatory cascade is also true 1) for ex vivo conditions in isolated renal proximal (S2) tubules from rabbit and 2) in a human renal epithelial cell line stably expressing human OAT1 (IHKE-hOAT1). EGF activated ERK1/2 in S2 tubules and IHKE-hOAT1, and, in both cases, ...
TY - JOUR. T1 - Functional analysis of rat renal organic anion transporter OAT-K1. T2 - Bidirectional methotrexate transport in apical membrane. AU - Masuda, Satohiro. AU - Takeuchi, Ayako. AU - Saito, Hideyuki. AU - Hashimoto, Yukiya. AU - Inui, Ken Ichi. PY - 1999/10/1. Y1 - 1999/10/1. N2 - Renal organic anion transporter OAT-K1 was stably transfected in MDCK cells and examined for its transport characteristics and membrane localization. OAT-K1 mediated both uptake and efflux of methotrexate in the apical membranes. Immunoblotting showed that the apparent molecular mass of the expressed OAT-K1 was 50 kDa, which was comparable to that found in the rat renal brush-border membranes. The OAT-K1-mediated methotrexate transport was significantly inhibited in the presence of several organic anions such as folate and sulfobromophthalein. These findings suggest that OAT-K1 mediates bidirectional methotrexate transport across the apical membranes, and may be involved in the renal handling of ...
Urate transport in the kidney proximal tubule is a bidirectional process. Although the urate reabsorption pathway has been elucidated recently, there is little knowledge about the excretory route. The basolateral organic anion transporters OAT1 and OAT3 presumably mediate uptake from blood into the cell, but for apical export from the cell into urine no candidate transporter has been identified. In this study, we show that the apical organic anion transporter MRP4 mediates ATP-dependent urate transport in isolated membrane vesicles and exports urate from transfected cells. Furthermore, the complex interaction pattern of urate with the MRP4 substrates MTX, cAMP, and cGMP indicates that MRP4 is an organic anion transporter with multiple allosteric binding sites.. Isolated apical and basolateral membrane vesicles from kidney proximal tubule have been used widely to study organic anion transport mechanisms, mainly using PAH or urate as a substrate (31). In contrast to basolateral membrane vesicles, ...
Figure 6. [3H]PAH efflux studies on X. laevis oocytes that were injected with water (mock) or hOAT4-cRNA. Three days after cRNA or water injection, 46 nl of a 200-μM [3H]PAH solution was injected into the oocytes, and efflux of [3H]PAH was measured, providing oocyte Ringers solution, chloride-free oocyte Ringers solution, and chloride-free oocyte Ringers solution plus 500 μM ES. The efflux was calculated as percentage of 3H content recovered in the supernatant compared with the sum of total radioactivity recovered in the medium and that remaining in the oocytes at the conclusion of a 30-min efflux period at room temperature, where hOAT4-expressing oocytes in oocyte Ringers solution were set to 100%, Data are means ± SEM or three independent experiments with five to seven oocytes each. **P , 0.01. ...
Anti-inflammatories are drugs that are used to reduce swelling and inflammation in the airways. For patients with conditions that cause inflammation in the lungs, such as chronic obstructive pulmonary disease (COPD) or asthma, anti-inflammatory drugs can make it easier to breathe. Most commonly, the anti-inflammatories used for lung conditions are steroids, specifically, corticosteroids or glucocorticosteroids. These steroids are not the same as the illegal anabolic steroids used to build muscles.. Steroid medications are most often inhaled using an inhaler. This delivers the drug directly to the lungs, which allows you to take a lower dose of the drug while still receiving a benefit. Steroids can also be taken orally in pill form, or in rare cases, intravenously. When steroids are taken orally, the dose must be higher than the dose in inhaled steroids. Some patients experience side effects from inhaled steroids, including bruising, oral infections, and hoarseness. Side effects from oral ...
Human organic anion transporter-1 (hOAT1) regulates the absorption, distribution, and excretion of a wide range of clinically important drugs. Our previous work demonstrated that hOAT1 is a dynamic membrane transporter, constitutively internalizing from and recycling back to the cell plasma membrane. Short-term activation (,30 minutes) of protein kinase C (PKC) promotes the attachment of a lysine 48-linked polyubiquitin chain to hOAT1, a process catalyzed by ubiquitin ligase neural precursor cell expressed developmentally down-regulated 4-2 (Nedd4-2). The ubiquitination of hOAT1 then triggers an accelerated endocytosis of the transporter from plasma membrane, which results in reduced hOAT1 expression at the cell surface and decreased hOAT1 transport activity. In the present study, we investigated the long-term effect of PKC on hOAT1. We showed that long-term activation (,2 hours) of PKC significantly enhanced hOAT1 degradation, and such action was partially blocked by ubiquitin mutant Ub-K48R, ...
Entecavir (ETV) is one of the most potent agents for the treatment of the hepatitis B viral infection. The drug is principally eliminated by the kidney. The goal of this study was to investigate the potential of ETV to interact in vitro with the renal SLC transporters hOAT1, hOCT2, hCNT2 and hCNT3. Potential drug-drug interactions of ETV at the renal transporters with antiviral drugs known to be excreted by the kidney (adefovir, tenofovir, cidofovir) as well as transporter-dependent cytotoxicity were also examined. Interactions with the selected transporters along with cytotoxicity were studied in several transiently-transfected cellular models using specific substrates and inhibitors. ETV was found to be both a substrate and inhibitor of hOAT1 (IC50 = 175.3 µM), hCNT2 (IC50 = 241.9 µM) and hCNT3 (IC50 = 278.4 µM) transporters, although it interacted with the transporters with relatively low affinities. ETV inhibited the cellular uptake of adefovir, tenofovir and cidofovir by hOAT1; however,
Human organic anion transporter 3 (hOAT3) belongs to a family of organic anion transporters that play critical roles in the body disposition of numerous clinically important drugs. In the current study, we examined the regulation of hOAT3 by peptide hormone bradykinin (BK) in COS-7 cells. BK (≤ 500 nM) induced a concentration- and time-dependent stimulation of hOAT3 activity, kinetically revealed as an increased Vmax. Such an increase in Vmax resulted from an increased cell surface expression without a change in total cell expression of the transporter. BK-induced stimulation of hOAT3 activity could be prevented by treating hOAT3-expressing cells with staurosporine, a general inhibitor for protein kinase C (PKC). To obtain further information on which PKC isoform mediates BK regulation of hOAT3 activity, cellular distribution of various PKC isoforms was examined in cells treated with BK. We showed that BK treatment resulted in a significant translocation of PKCδ, PKCϵ and PKCζ from cytosol ...
OATs belong to the solute carrier 22 transport protein superfamily, and they transport small, amphiphilic organic anions of diverse chemical structures. OAT1, the first OAT to be cloned, is strongly expressed in human kidney and localized at the basolateral membrane of the proximal tubule (Hosoyamada et al., 1999). OAT1 is known to play a central role in the renal uptake of a wide range of anionic xenobiotics, including endogenous metabolic waste products, environmental toxins, and numerous clinically important drugs (e.g., antibiotics, antivirals, anti-inflammatory drugs, diuretics, and anticancer agents) (Rizwan and Burckhardt, 2007; Burckhardt, 2012; Wang and Sweet, 2013b). In addition, OAT1 is involved in the development of nephrotoxicity of many anionic xenobiotics (Hagos and Wolff, 2010). Consequently, preloading of OAT1 inhibitors, including probenecid, betamiprone, and NSAIDs, has been reported to reduce OAT1-mediated drug nephrotoxicity (Tune et al., 1977; Hirouchi et al., 1994; Lacy et ...
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Organic anions of diverse chemical structures are secreted in renal proximal tubules. The first step in secretion, uptake of organic anions across the basolateral membrane of tubule cells, is...
The OAT (organic anion transporter) family mediates the absorption, distribution and excretion of a diverse array of environmental toxins and clinically important drugs. OAT dysfunction significantly contributes to renal, hepatic, neurological and fetal toxicity and disease. As a first step to establish the topological model of hOAT1 (human OAT1), we investigated the external loops and the cellular orientation of the N- and the C-termini of this transporter. Combined approaches of immunofluorescence studies and site-directed chemical labelling were used for such purpose. Immunofluorescence microscopy of Myc-tagged hOAT1 expressed in cultured cells identified that both the N- and the C-termini of the transporter were located in the cytoplasm. Replacement of Lys59 in the predicted extracellular loop I with arginine resulted in a mutant (K59R), which was largely inaccessible for labelling by membrane-impermeable NHS (N-hydroxysuccinimido)-SS (dithio)-biotin present in the extracellular medium. This ...
For many the diagnosis of histamine intolerance or mast cell activation will come after decades of mis-diagnosis. Some of us will have been told its psychosomatic and prescribed antidepressants, benzodiazepines and sleeping pills, while others may have been told their severe gastrointestinal issues are caused by stomach bacteria, or chronic stuffed nose and frequent flu-like events caused by sinus/staph infection, or that their urinary burning and frequency is caused by a UTI and prescribed interminable courses of antibiotics.. I was told I had all of these and prescribed antibiotics, even when bacterial cultures came back negative.. What I wasnt told is that many antibiotics exert an anti-inflammatory effect on the body, independently of their activity as an antibiotic [1].. As an example: lets break down how this information could have prevented my being prescribed a daily dose of the antibiotic Macrobid (Nitrofurantoin), for a chronic, but non-existent urinary tract infection that I now ...
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Inflammation is your bodys natural response to injury or infection and manifests in the form of redness, heat or swelling in a localised area. Acute inflammation is the initial protective response of your body to injury or infection, and is designed to heal the body and restore normal tissue function. If inflammation persists, it shifts into the basket of chronic inflammation, and can be the result of a prolonged infection, autoimmune reaction or allergy.. Before you race into the chemist for an over-the-counter anti-inflammatory, check your pantry for the amazing natural anti-inflammatories discussed below. Such natural remedies used to be, and in some places still are, the foundation of traditional medicine. We are beyond happy to see these making a rise again in the health world, not only for treating health ailments, but for working in the prevention of such health issues before they arise. Check out how easy it can be to include anti-inflammatories in your daily intake without ...
My ten year old dog has episodes lasting several weeks where he becomes very weak to the point he cant walk more than about thirty feet before his legs start shaking and he needs to lie down and rest for several minutes before getting up to continue walking, and he cant climb the stairs. The first time coincided with a fall down the stairs, so we thought hed hurt his back - brought him to the vet for X-rays and the vet saw nothing unusual, all bones and joints looked good, no signs of arthritis or unusual positions or spacing, so concluded it was a "soft tissue injury" of some sort and prescribed anti-inflammatories and pain meds. After several days, he fully recovered. Now, about six months later, he had the same symptoms but with no trauma preceding it, so initially we figured hed aggravated the injury and brought him back. Two weeks of anti-inflammatories and pain meds showed no improvement, so brought him back for more x-rays. The vet saw nothing and referred us to a veterinary teaching ...
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I am just come off of steroids that were giving to me for a pinched nerve. I was on a tapering dose. I took 6 pills the first day, 5 pills the second day, and so on and so forth. I took my last one yesterday and I have to tell you, I feel like a balloon. I am a heavy person anyway--but I feel very bloated. I guess that is also a side effect of the anti-inflammatory medication. Besides the fact that they make me *feel* hungry ...
I am just come off of steroids that were giving to me for a pinched nerve. I was on a tapering dose. I took 6 pills the first day, 5 pills the second day, and so on and so forth. I took my last one yesterday and I have to tell you, I feel like a balloon. I am a heavy person anyway--but I feel very bloated. I guess that is also a side effect of the anti-inflammatory medication. Besides the fact that they make me *feel* hungry ...
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Information for patients on this group of medications which have pain-relieving (analgesic) effects and reduce inflammation when used over a period of time. NSAIDs include aspirin, ibuprofen, and diclofenac. ...
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Fatigue, low energy, aches & pains? You may be struggling with chronic inflammation, an ongoing activation of your immune system.
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PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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Clinical signs presented as a typical respiratory infection including a deep chested rattle. Initially antibiotic therapy was given with little improvement, however when a long acting anti-inflammatory injection was given the clinical signs appeared to be alleviated very quickly. These same signs would occur once more approximately 3-4 weeks later when the anti-inflammatory effects began to lessen. The treatment of anti-inflammatories and antibiotics were given when needed. The antibiotics used in varying combination were Baytril, doxycycline and Zithromax. Over the next few months the chest rattle was occurring more frequently and eventually stopped disappearing completely even with the injections of an anti-inflammatory agent. During this period she was perfectly healthy in every other aspect of her life. The decision was made by the vet to take x-rays of Lilys chest to rule out the possibility of masses within her lungs which might be causing the clinical signs seen. X-rays were taken and a ...
Yet that wonderful gadget, connecting you to so many fascinating facts, people, news items, apps, gossip and image-defining feedback, may be surreptitiously, progressively chipping away at your health, hormones, sexual performance, brain function and longevity. It may feel like your lifeline, but what if its actually causing serious problems that youre blaming on something else? What if youre taking sleeping pills, painkillers, anti-seizure drugs, anti-inflammatories or other pharmaceuticals to address something thats being caused by your wireless wonder-phone? It is, after all, emitting a powerful signal that extends for 20-40 feet in all directions around you. Invisible and intangible (to most), yet capable of penetrating cement, metal, plastic, rubber, clothing and human bodies, this radiation is the ultimate silent, stealthy, insidious invader. Youll never see it coming, and it will be the last thing youll ever think of blaming if youre sick, exhausted, have cancer, become infertile, ...