PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “AMINOHIPPURIC ACID”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources

Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain.

A cDNA encoding the new member of the multispecific organic anion transporter family, OAT3, was isolated by the reverse transcription-polymerase chain reaction cloning method. Degenerate primers were designed based on the sequences conserved among OAT1, OAT2, and organic cation transporter 1 (OCT1), and reverse transcription-polymerase chain reaction was performed using rat brain poly(A)+ RNA. The 536-amino acid protein sequence encoded by OAT3 showed 49, 39, and 36% identity to those of OAT1, OAT2, and OCT1, respectively. Northern blot analysis revealed that rat OAT3 mRNA is expressed in the liver, brain, kidney, and eye. When expressed in Xenopus laevis oocytes, OAT3 mediated the uptake of organic anions, such as p-aminohippurate (Km = 65 microM), ochratoxin A (Km = 0.74 microM), and estrone sulfate (Km = 2.3 microM) and a cationic compound, cimetidine. OAT3-mediated uptake of [3H]estrone sulfate was sodium-independent. para-Aminohippuric acid, estrone sulfate or ochratoxin A did not show any trans-stimulatory effect on either influx or efflux of [3H]estrone sulfate via OAT3. Organic anions such as sulfobromophthalein, probenecid, indocyanine green, bumetanide, piroxicam, furosemide, azidodeoxythymidine, 4, 4'-diisothiocyanostilbene-3,3'-disulfonic acid, and benzylpenicillin inhibited OAT3-mediated estrone sulfate uptake, while ouabain and digoxin did not. Organic cations such as tetraethylammonium, guanidine, verapamil, and quinidine did not interact with OAT3. Acidic metabolites of neurotransmitters derived from dopamine, epinephrine, norepinephrine, and serotonin inhibited the uptake of estrone sulfate via OAT3. These results suggest an important role of OAT3 in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain.

Amino Acid Sequence↗

Characterization of salicylate uptake across the basolateral membrane of the malpighian tubules of Drosophila melanogaster.

The organic anion salicylate is a plant secondary metabolite that can protect plants against herbivores. Transport of salicylate across the basolateral membrane of the Malpighian tubules of Drosophila melanogaster was studied using a radioisotope tracer technique. The uptake of [(14)C]salicylate by the Malpighian tubules was active, saturable and Na(+)-dependent; the maximum uptake rate (J(max)) and the half saturation concentration (K(t)) were 12.6 pmoltubule(-1)min(-1) and 30.7micromoll(-1), respectively. In contrast to organic anion transport by vertebrate renal tissues, salicylate uptake was not trans-stimulated by glutarate (0.01-1.0 mmoll(-1)) or cis-inhibited by high concentrations (5 mmoll(-1)) of various alpha-keto acids (glutaric acid, alpha-ketoglutaric acid, succinic acid, and citric acid). Changes in basolateral membrane potential or physiologically relevant changes in bathing saline pH did not affect the rate of [(14)C]salicylate uptake. Ring-structure monocarboxylic acids (benzoic acid, nicotinic acid, gentisic acid, unlabelled salicylic acid, alpha-cyano-4-hydroxycinnamic acid, probenecid, fluorescein, and P-aminohippuric acid) strongly inhibited [(14)C]salicylate uptake rate. In contrast, short-chain monocarboxylic acids had little (butyric acid) or no effect (lactic acid, pyruvic acid, and propionic acid). Our results suggest that salicylate uptake across the basolateral membrane of D. melanogaster Malpighian tubules is mediated by a non-electrogenic, alpha-cyano-4-hydroxycinnamic acid-sensitive, Na(+):salicylate cotransport system.

Animals↗

Renal tolerance for ioxaglate in patients with chronic renal failure.

The authors sought to evaluate renal tolerance for ioxaglate sodium meglumine used as a contrast agent in patients with chronic renal failure. Eight male patients (mean age, 55 years +/- 5) with chronic renal insufficiency (glomerular filtration rate less than 60 mL/min) who underwent diagnostic cardiac catheterization were enrolled. Renal clearance of inulin and rho-aminohippuric acid and urinary enzyme excretion were studied 1 day before and 1 day after administration of 167 mL +/- 43 of ioxaglate. None of the patients experienced any adverse reactions. All the patients had markedly depressed renal clearance values before angiography. Mean serum creatinine level, glomerular filtration rate, effective renal plasma flow, and urinary beta 2-microglobulin excretion were unaltered by angiography. After the procedure, only one patient had an increase in serum creatinine level of more than 10% (from 115 to 159 mumol/L [1.3 to 1.8 mg/dL]), with a decrease in glomerular filtration rate from 34 to 27 mL/min. In this patient, serum creatinine level and glomerular filtration rate normalized within 72 hours. Using accurate and sensitive renal function tests, the authors have shown that ioxaglate may be used safely in patients with chronic renal failure.

Adult↗

Kinetic analysis of the renal handling of 2,2-bis(p-chlorophenyl) acetic acid by the rat.

The kinetics of uptake and efflux of organic acids in rat renal cortical slices were used to examine the affinity of 2,2-bis(p-chlorophenyl)acetic acid (DDA) for the organic acid transport system and to assess intracellular binding of this polar 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) metabolite. As judged by its ability to inhibit p-aminohippuric acid transport, DDA was a potent competitive inhibitor, almost as strong as probenecid, the classical inhibitor of this system. Efflux of DDA from slices demonstrated that the bulk (85%) of the DDA within the slice was reversibly bound to proteins or other macromolecules. Cortical slices incubated 60 minutes with 10 micron DDA contained a total concentration of 160 micron DDA within the tubular cells, but the actual free concentration in the cells was only 20 to 30 micron. Thus, although DDA was accumulated against a concentration gradient by the kidney, the gradient was much smaller than the measured tissue/medium ratio. Potential consequences of DDA exposure through its interaction with the organic acid system and roles of DDA binding sites in the toxicity and transport of DDA are discussed.

Animals↗

Interaction of structurally similar pesticides with organic anion transport by primary cultures of winter flounder renal proximal tubule.

We assessed the interaction of several pesticides with renal organic anion transport based on inhibition of the active transepithelial transport of p-aminohippuric acid ([3H]PAH) by primary cultures of winter flounder proximal tubules. Four structurally similar chlorophenoxy acid herbicides were tested. 2-Methyl-4-chlorophenoxyacetic acid at 0.1 mM had no effect on PAH transport. 2-(2,4-Dichlorophenoxy)propionic acid, 2-(2-methyl,4-chlorophenoxy)propionic acid and 2,4-dichlorophenoxyacetic acid inhibited PAH secretion with IC50 values (median inhibitory concentrations) of 0.09, 0.2 and 0.2 mM, respectively. At 2-(2-methyl,4-chlorophenoxy)propionic acid concentrations of 10(-7) to 10(-6) M, PAH secretion was stimulated to 132 and 139% of controls, respectively, at 2 hr. 2,2-bis-p-Chlorophenylacetic acid was tested at concentrations of 10(-7) to 10(-3) M and inhibited with an IC50 of 0.02 mM. At 10(-7) M 2,2-bis-p-chlorophenylacetic acid, a delayed increase was again seen in which PAH secretion increased to 154% of control at 2 hr. The anticholinesterase insecticide phosphothioic acid O,O-diethyl-O-(3,5,6-trichloro-2-pyridinyl ester), its more active metabolite O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl)phosphate and its dimethyl analog, phosphothioic acid O,O-dimethyl-O-(3,5,6-trichloro-2-pyridinyl ester) were tested at 0.1 mM. Phosphothioic acid O,O-diethyl-O-(3,5,6-trichloro-2-pyridinyl ester) increased PAH secretion significantly to 115% of control whereas the O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl)phosphate inhibited by 28%.(ABSTRACT TRUNCATED AT 250 WORDS)

2,4-Dichlorophenoxyacetic Acid↗

Transport of prostaglandins and other eicosanoids by the choroid plexus: its characterization and physiological significance.

Choroid plexi from the lateral ventricles of rabbits, cats, and dogfish (Mustelus canis) were used to characterize the prostaglandin (PG) uptake process and to establish its kinetic parameters and substrate specificity. The apparent Kt for PGF2 alpha transport by the rabbit choroid plexus was 20 microM; the Jmax was 27 nmol g-1 min-1. The Ki of inhibition of PGF2 alpha transport by PGE2 was 20 microM; the Jmax of PGF2 alpha transport was unaltered by PGE2. A concentration of p-aminohippuric acid of up to 1 mM did not appreciably affect the Kt or the Jmax of PGF2 alpha transport. The rate of PGF2 alpha accumulation by rabbit choroid plexus was reduced by incubation at 4 degrees C, under anaerobic conditions, in the absence of sodium or in the presence of ouabain, probenecid, or bromcresol green. The choroid plexi of all three species also accumulated thromboxane B2, PGI2, and 6-keto-PGF1 alpha, suggesting that most, if not all, eicosanoids are substrates for this transport system. It is concluded that the choroid plexus transport system satisfies all the criteria of an active, energy-dependent transport system and that this system functions effectively at concentrations of eicosanoids present in the ventricular system under normal or pathological conditions. Hence, this transport system must make an important contribution to the pharmacokinetics of eicosanoids within the brain.

6-Ketoprostaglandin F1 alpha↗

Severe hyperglycemia: a determinant factor for hypofiltration in alloxan diabetic rats.

The relationships among glomerular filtration rate, renal plasma flow and extracellular fluid volume were investigated in control and severely hyperglycemic (442+/-33 mg/dl) untreated, alloxan diabetic ats. Most of diabetic animals showed significant lower values of inulin clearance (diabetics, 0.55+/-0.07 ml/min.100 g; controls, 0.97+/-0.04) and p-aminohippurate clearance (diabetics, 2.11+/-0.39 ml/min.100 g; controls, 3.93+/-0.25). Diabetic rats exhibited reduced efficiency in tubular Na(+) reabsorption, increased urinary Na(+) excretion (diabetics, 3.12+/-0.27 mEq/day; controls, 1.25+/-0.14) and diminished values of plasma renin activity (diabetics, 3.34+/-0.44 ng/ml.h; controls, 8.64+/-0.79). Significant negative correlations were found between glycemia and renal hemodynamic variables. Acute overload with glucose further decreased these variables in both groups: inulin clearance in diabetics vs. controls, 0.26+/-0.04 vs. 0.44+/-0.05 ml/min.100 g; p-aminohippuric acid clearance in diabetics vs. controls, 1.09+/-0.20 vs. 1.55+/-0.21 ml/min.100 g. We conclude that chronically hyperglycemic alloxan diabetic rats showed diminished glomerular filtration rates (inulin clearance), renal plasma flow ( p-aminohippurate clearance) and extracellular fluid volume associated with urinary Na(+) losses and alterations in the renin-angiotensin system. Decreased renin-angiotensin system activity might reduce aldosterone secretion, which in turn could result in (successively) urinary sodium loss, extracellular fluid volume contraction and reductions in glomerular filtration and renal plasma flow.

Animals↗

Mercapturic acids (N-acetylcysteine S-conjugates) as endogenous substrates for the renal organic anion transporter-1.

Mercapturic acids are N-acetyl-L-cysteine S-conjugates that are formed from a range of endogenous and exogenous chemicals. Although the kidney is a major site for elimination of mercapturic acids, the transport mechanisms involved have not been identified. The present study examined whether mercapturic acids are substrates for the renal basolateral organic anion transporter-1 (Oat1) from rat kidney. This carrier mediates uptake of organic anions from the bloodstream in exchange for intracellular alpha-ketoglutarate. Uptake of [(3)H]p-aminohippuric acid (PAH) in Oat1-expressing Xenopus laevis oocytes was strongly inhibited by S-(2,4-dinitrophenyl)-N-acetyl-L-cysteine (DNP-NAC) and by all other mercapturic acids tested, including the endogenous mercapturic acid N-acetyl-leukotriene E(4). Inhibition by the mercapturic acids was competitive, which is consistent with the hypothesis that these compounds are substrates for Oat1. This conclusion was supported by the direct demonstration of saturable [(35)S]DNP-NAC uptake in Oat1-expressing oocytes. [(35)S]DNP-NAC uptake was inhibited by PAH and other mercapturic acids and was stimulated in oocytes preloaded with glutarate. The apparent K(m) value for DNP-NAC uptake was only 2 microM, indicating that this mercapturic acid is a high affinity substrate for Oat1. Together, these data indicate that clearance of endogenous mercapturic acids is an important function of the renal organic anion transporter.

Acetylcysteine↗

Evaluation of renal function in transplant patients on tacrolimus therapy.

Glomerular filtration rate (GFR), as measured by 24-hour creatinine clearance and clearance of iothalamate, and effective renal plasma flow (ERPF), as measured by the clearance of para-aminohippuric acid (PAH), were evaluated at 2 weeks, 1 month, and 3 months after transplantation in 8 renal transplant patients and at 1 month and 1 year after transplantation in 9 liver transplant patients receiving tacrolimus (Prograf) therapy. In renal transplant patients, there was a significant increase in GFR after transplantation. There was no change in GFR at 1 and 3 months as compared to 2 weeks after transplantation, while ERPF (ml/min/1.73 m2) was lower (p < 0.05) at 3 months (212+/-42) compared to 1 month (306+/-118) after transplantation. In liver transplant patients, GFR and ERPF were below normal despite normal serum creatinine concentrations, but there was no difference in GFR or ERPF at 1 month and 1 year after transplantation. Although below normal, renal function was well preserved in transplant patients while receiving chronic tacrolimus therapy over the study period. Dosage alterations ofrenally eliminated drugs may be required for drugs with a narrow therapeutic index.

Adult↗

Effect of oxygen toxicity and nitric acid-induced lung damage on drug absorption from the rat lung.

To investigate the effect of pulmonary oxygen toxicity and nitric acid-induced lung damage on absorption of drugs from the lung, rats were either exposed continuously to approximately 100% oxygen or given an intratracheal injection of 1% nitric acid solution (0.15 ml), and rates of drug absorption from damaged and control lungs were compared after various times. To measure pulmonary absorption rates, 0.1 ml of drug solution (0.1-10 mM) was administered through a tight-fitting tracheal cannula to anesthetized animals, and, after various times, lungs were assayed for unabsorbed drug. Drugs investigated were procaine amide ethobromide, p-aminohippuric acid, procaine amide and mannitol-14C. Rates of drug absorption were increased 1.1-1.2 fold after 48-54 hrs of continuous oxygen exposure and 1.3-1.6 fold at 1-4 days after nitric acid treatment. The results suggest that both types of lung damage increase the porosity of the absorbing membrane, and that nitric acid damage also alters the integrity of lipoid regions of the membrane.

Absorption↗

Plasma clearance in the rat of a furan dicarboxylic acid which accumulates in uremia.

The furan dicarboxylic acid 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (5-propyl FPA) accumulates in the plasma of patients with chronic renal failure and has been implicated in several aspects of the uremic syndrome: the defective binding of organic acids in uremic plasma, inhibition of active tubular secretion, anemia and the severity of neurological symptoms. Evidence from experiments with rat kidney slices suggests that 5-propyl FPA undergoes active tubular secretion, and so its clearance after an intravenous bolus dose (5 mg/kg; 21 mumol/kg) was investigated in anaesthetized female Wistar albino rats in vivo. The effects of intravenous bolus doses of p-aminohippuric acid (PAH) and probenecid on the clearance of this dose of 5-propyl FPA were also studied. The mean values (N = 16) for plasma half-life, plasma clearance and apparent volume of distribution of 5-propyl FPA were 3.6 hours, 2.4 ml . min(-1) . kg(-1) and 0.69 liter . kg(-1), respectively. An equimolar dose of PAH did not affect the clearance of 5-propyl FPA, but a tenfold higher molar dose of PAH (40.4 mg/kg) increased the area under the plasma-concentration time curve of 5-propyl FPA, and there was a trend towards a decrease in the clearance and a prolongation of the half-life. Probenecid at a fivefold higher dose than 5-propyl FPA had a similar effect to PAH and increased the AUC of 5-propyl FPA. PAH and probenecid decreased the plasma clearance of 5-propyl FPA, which is evidence that this uremic metabolite undergoes active tubular secretion. It follows that 5-propyl FPA could therefore inhibit the secretion of other organic acids.

Animals↗

Captopril augments the renal response to an amino acid infusion in diabetic adults.

This study examined whether patients with insulin-dependent diabetes mellitus and normal renal function have an altered response to an amino acid infusion when they are pretreated with a converting-enzyme inhibitor. Three groups of adults received amino acid infusions for 20 min on two occasions separated by a 240-min interval. Groups 1 (6 normals) and 2 (6 diabetics) ingested captopril (12.5 mg) 120 min before starting the second infusion. Group 3 (4 diabetics) did not receive captopril. Diabetics had normal base-line renal plasma flow, as indicated by para-aminohippuric acid clearance (CPAH), and glomerular filtration rate (GFR). In group 1, the maximum increase in CPAH was significant and similar with both infusions, 23 +/- 5 vs. 15 +/- 3% (SE); maximal changes in GFR were also significant and similar, 20 +/- 5 vs. 20 +/- 6%. In Group 2, the maximal increase in CPAH and GFR with the first infusion was 28 +/- 7 and 23 +/- 6%, respectively. After captopril, the increases in CPAH and GFR were significantly greater than with the first infusion (64 +/- 8%, P less than 0.002, and 67 +/- 9%, P less than 0.002, respectively). In Group 3 diabetics, there was no difference in either CPAH or GFR with the first vs. the second infusion. Thus captopril enhances the renal hemodynamic response to an amino acid load in diabetic patients but not in normal adults.

Adult↗

Determination of efficacy of linotroban by inducing a reduction of renal inulin/para-aminohippuric acid clearances with the thromboxane A2 mimetic U-46619 in the conscious female rat.

Linotroban (CAS 141443-73-4), a potent and selective thromboxane (TXA2) receptor antagonist, is known as a novel antithrombotic agent. It is suggested that pharmacological inhibition of TXA2 synthesis or action merits continued evaluation in the treatment of a variety of renal diseases. The aim of this study was the determination of efficacy of this new TXA2 receptor antagonist by assessing its effect on the reduction in inulin and para-aminohippuric acid (PAH) clearances induced by the TX/prostaglandin endoperoxide mimetic U-46619 in the conscious female rats. The following doses (3, 10, 30 mg/kg/24 h) of linotroban mixed with 720 micrograms TX-mimetic U-46619/kg/24 h were administered via osmotic pumps at a delivery rate of 10 microliters/h, implanted s.c. during 72 h. Rats of the U-46619 group were administered 720 micrograms U-46619/kg/24 h alone as described above, controls received 3.5% NaHCO3, respectively. Inulin/PAH clearances were determined at the end of the 4-h clearance period (68 h-72 h). Summarizing the data, glomerular filtration rate (GFR) and PAH clearances were reduced significantly by U-46619. When linotroban (3, 10 or 30 mg/kg/24 h) was added to U-46619 the GFR and PAH clearance were reversed to values that showed no significant differences to the controls.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Plasma 5-hydroxyindoleacetic acid as an endogenous index of renal plasma flow.

5-Hydroxyindoleacetic acid (5-HIAA), the major serotonin metabolite, was measured in human plasma and urine using liquid chromatography and electrochemical detection. The renal extraction of 5-HIAA was 78%, a value compatible with an almost complete extraction during a single passage of the blood through the kidney. In addition, plasma levels of 5-HIAA measured in patients with a wide range of renal function was inversely correlated (r = 0.85) with the clearance of para-aminohippuric acid (PAH). The results indicate that 5-HIAA determinations can be used as an alternative procedure to the PAH clearance method for the estimation of renal plasma flow in clinical practice.

Adult↗

Inhibition of the efflux of organic ions from renal cortical slices.

Cyanine 863 inhibited the efflux of tetraethylammonium ion from slices of rat or rabbit renal cortex while the efflux of p-aminohippuric acid was unaffected. Dinitrophenol increased the efflux rate of both the cation and anion. Cyanine also decreased the dinitrophenol-enhanced efflux of tetraethylammonium (TEA).

Aminohippuric Acids↗

Rat organic anion transporter 3 (rOAT3) is responsible for brain-to-blood efflux of homovanillic acid at the abluminal membrane of brain capillary endothelial cells.

The mechanism that removes homovanillic acid (HVA), an end metabolite of dopamine, from the brain is still poorly understood. The purpose of this study is to identify and characterize the brain-to-blood HVA efflux transporter at the rat blood-brain barrier (BBB). Using the Brain Efflux Index method, the apparent in vivo efflux rate constant of [3H]HVA from the brain, k(eff), was determined to be 1.69 x 10(-2) minute(-1). This elimination was significantly inhibited by para-aminohippuric acid (PAH), benzylpenicillin, indoxyl sulfate, and cimetidine, suggesting the involvement of rat organic anion transporter 3 (rOAT3). rOAT3-expressing oocytes exhibited [3H]HVA uptake (K(m) = 274 micromol/L), which was inhibited by several organic anions, such as PAH, indoxyl sulfate, octanoic acid, and metabolites of monoamine neurotransmitters. Neurotransmitters themselves did not affect the uptake. Furthermore, immunohistochemical analysis suggested that rOAT3 is localized at the abluminal membrane of brain capillary endothelial cells. These results provide the first evidence that rOAT3 is expressed at the abluminal membrane of the rat BBB and is involved in the brain-to-blood transport of HVA. This HVA efflux transport system is likely to play an important role in controlling the level of HVA in the CNS.

Animals↗

Effects of azotemia on renal extraction and clearance of PAH and TEA.

Dogs were made azotemic by bilateral ureteral-venous anastomosis. Subsequently, the left ureter, a systemic artery, and the left renal vein were cannulated. Left renal blood flow (RBF) was measured by an electromagnetic flowmeter. Left renal clearances and extractions of [14C]tetraethylammonium ([14C]TEA) and p-aminohippuric acid (PAH) were determined at five 40-min intervals after administraiton of loading doses and institution of a maintenance infusion containing PAH and [14C]TEA. The renal extraction of TEA was independent of blood urea nitrogen (BUN), whereas the extraction of PAH correlated inversely with BUN. Renal plasma flows calculated from urinary clearances and renal extractions agreed with renal plasma flows calculated from flowmeter data. The extraction of TEA remained constant over the 200-min experimental period, whereas the extraction of PAH increases progressively as a function of time. It is probable that those organic acids which accumulate in azotemia, and interfered with renal tubular secretion of PAH, were themselves eliminated after opening the ureteral-venous anastomosis. Thus, TEA is superior to PAH for evaluation of the renal circulation in azotemia.

Aminohippuric Acids↗

Role of blood-brain barrier organic anion transporter 3 (OAT3) in the efflux of indoxyl sulfate, a uremic toxin: its involvement in neurotransmitter metabolite clearance from the brain.

Renal impairment is associated with CNS dysfunctions and the accumulation of uremic toxins, such as indoxyl sulfate, in blood. To evaluate the relevance of indoxyl sulfate to CNS dysfunctions, we investigated the brain-to-blood transport of indoxyl sulfate at the blood-brain barrier (BBB) using the Brain Efflux Index method. [(3)H]Indoxyl sulfate undergoes efflux transport with an efflux transport rate of 1.08 x 10(-2)/min, and the process is saturable with a Km of 298 microm. This process is inhibited by para-aminohippuric acid, probenecid, benzylpenicillin, cimetidine and uremic toxinins, such as hippuric acid and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid. RT-PCR revealed that an OAT3 mRNA is expressed in conditionally immortalized rat brain capillary endothelial cell lines and rat brain capillary fraction. Xenopus oocytes expressing OAT3 were found to exhibit [(3)H]indoxyl sulfate uptake, which was significantly inhibited by neurotransmitter metabolites, such as homovanillic acid and 3-methoxy-4-hydroxymandelic acid, and by acyclovir, cefazolin, baclofen, 6-mercaptopurine, benzoic acid, and ketoprofen. These results suggest that OAT3 mediates the brain-to-blood transport of indoxyl sulfate, and is also involved in the efflux transport of neurotransmitter metabolites and drugs. Therefore, inhibition of the brain-to-blood transport involving OAT3 would occur in uremia and lead to the accumulation of neurotransmitter metabolites and drugs in the brain.

Animals↗