• Childhood Kidney Diseases
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• v.14 no.2
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• pp.120-131
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• 2010

Renal tubular acidosis (RTA) is a metabolic acidosis due to impaired excretion of hydrogen ion, or reabsorption of bicarbonate, or both by the kidney. These renal tubular abnormalities can occur as an inherited disease or can result from other disorders or toxins that affect the renal tubules. Disorders of bicarbonate reclamation by the proximal tubule are classified as proximal RTA, whereas disorders resulting from a primary defect in distal tubular net hydrogen secretion or from a reduced buffer trapping in the tubular lumen are called distal RTA. Hyperkalemic RTA may occur as a result of aldosterone deficiency or tubular insensitivity to its effects. The clinical classification of renal tubular acidosis has been correlated with our current physiological model of how the nephron excretes acid, and this has facilitated genetic studies that have identified mutations in several genes encoding acid and base ion transporters. Growth retardation is a consistent feature of RTA in infants. Identification and correction of acidosis are important in preventing symptoms and guide approved genetic counseling and testing.

• Archives of Pharmacal Research
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• v.17 no.2
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• pp.124-130
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• 1994

Plasma phamacokinetics and renal excretion of theophylline (TP) and its metabolities were ivnestigated in rats. Plasma concentrations of TP declined in a monoexponential manner, while those of 1-methyluric (MU) and 1,3-dimethyluric(DMU) declined in a biexponential manner upon respective iv bolus injection of each compound at 6mg/kg dose. The total body clearances $(CL_r)$ of the metabolites were 4-6 fold larger than that of TP, while the distribution volumes of them at steady-state $(Vd_{ss})$ were 40-50% smaller than that of TP. The metabolites showed their plasma peaks in 30 min after iv injection of TP indicating than that to MU. Renal excretion of TP and its metabolites was studied in urine flow rate (UFR)-controlled rats. The renal clearance $(CL_r)$ of TP was inversely related to pasma TP concentrations, and much smaller than the glomerular filtration rate (GFR) suggesting tubular secretion and profound reabsorption in the renal tubule. The $(CL_r)$ of each metabolite also showed that inverse relationship, but far exceeded GFR suggesting that tubular secretion than GFR by ip injection of probenecid (142.7 mg/kg). It supports that the metabolies are secreted in the renal tubule, and suggests that they share a common transport system in their sectrtion processes with probenecid. On the other hand, the $(CL_r)$ of TP was not affected significantly by the probenecid treatment. Considering the inverse relationship of TP between the $(CL_r)$ and its ploasma concentrations,no effect of probenecid on $(CL_r)$ of TP is most likely due to negligible contribution of the secretion to the overall $(CL_r)$ of TP.

• Korean Journal of Veterinary Research
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• v.7 no.2
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• pp.51-55
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• 1967

The mammary excretion of suphamethomidine after intravenous and/or oral administration was investigated in cow. The results show that sulphamethomidine is bound to plasma proteins to a great extent (80~90%). Ay a dosage of 60 mg./kg. maximal concenration in plasma of this sulphonamide was reached 7-10 hours after oral dosing. The sulphonamide concentration in plasma slowly declined after both oral and intravenous administration (fig. 1, 2, and 3) The concentration of sulphonamide in milk was very low and the excretion was completed in 7 days after a single oral dose and 5 days after intravenous injection while in the case of blood plasma it was 11 and 7 days, respectively. In addition, the renal excretion of sulphamethomidine was investigated while under continuous intravenous intravenous infusion. The excretion ratios varies according to self depression (table. 1). Blockade of the tubular secretion with diodone lowered the excretion of sulphamethomidine. It is concluded that the renal excretion of sulphamethomidine in cows occurs by filtration by slight tubular secretion and also by a high rate of back diffusion.

• The Korean Journal of Physiology
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• v.16 no.2
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• pp.177-186
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• 1982

The effect of ethacrynic acid (EA) on the renal secretion of PAH was examined in cat kidney. $C_{PAH}$ and $T_{PAH}$ were measured before and after infusion of EA $(0.5{\sim}50mg/kg)$ through the femoral vein. The following results were obtained: 1) In the dosage range of 0.5 to 25 mg/kg, EA increased the urine flow, and sodium and potassium excretion in dose-dependent manner, but the glomelular filtration rate was decreased as the dosage of EA was increased. 2) $C_{PAH}$ and $T_{PAH}$ were decreased by EA in the dosage range of 3 to 25 mg/kg and 1 to 50 mg/kg, respectively, in dose·dependent manner with the dosage to cause 50% inhibition of about 5 mg/kg. 3) With dosage of 0.5mg/kg, EA appeared to exert a great effect on diuretic response without the influence on $T_{PAH}$. At 10min after infusion of EA, a potent diuretic effect appeared, while $T_{PAH}$ did not show a significant change. These results suggest that the action mechanism of EA on tubular secretion of PAH may be different from that on natriuresis. 4) With dosage of 5 mg/kg, EA did not inhibit the Na-K-ATPase activity in microsomal fractions from both cortex and medulla. 5) The double reciprocal plot ($l/T_{PAH}$ versus $l/P_{PAH}$) suggested that EA inhibited the P AH secretion by a competitive pattern. However, probenecid, a prototypic inhibitor of the organic acid pump, had no influence on both the inhibitory effect of $T_{PAH}$ and the natriuretic effect by EA. These results suggest that in vivo EA altered tubular secretion of P AH through interactions with receptors that are not identical with the Na-K-ATPase.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.41-46
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• 2002

Effect of cadmium (Cd) intoxication on renal acid-base regulation was studied in adult male Sprague-Dawley rats. Cd intoxication was induced by subcutaneous injections of $CdCl_2$ at a dose of 2 mg Cd/kg/day for $3{\sim}4$ weeks. In Cd-intoxicated animals, arterial pH, $PCO_2$ and plasma bicarbonate concentration decreased, showing a metabolic acidosis. Urine pH and urinary bicarbonate excretion increased and titratable acid excretion decreased with no change in ammonium excretion. In renal cortical brush-border membrane vesicles derived from Cd-exposed animals, the $Na^+/H^+$ antiporter activity was significantly attenuated. These results indicate that chronic exposures to Cd impair the proximal tubular mechanism for $H^+$ secretion (i.e., $Na^+/H^+$ antiport), leading to a metabolic acidosis.

• Journal of Pharmaceutical Investigation
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• v.21 no.1
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• pp.33-41
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• 1991

A high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of theophylline(TP) and its metabolites, 1-methyluric acid (1-MU) and 1,3-dimethyluric acid (1,3-DMU), in rat plasma and urine. An $100\;{\mu}l$ aliquot of a plasma or urine sample was mixed with $250\;{\mu}l$ of acetonitrite and vortexed. After centrifugation, $200\;{\mu}l$ (plasma) or $20\;{\mu}l$ (urine) aliquot of the supernatant was dried by $N_2$ stream and redissolved in $100\;{\mu}l$ (plasma) or $200\;{\mu}l$ (urine) of the mobile phase. A $20\;{\mu}l$ of the mobile phase solution was injected onto a $C_{18}$ reversed-phase column. The column was maintained at $45^{\circ}C$ by the aid of electric heating jacket. The mobile phase was a 3%(v/v) methanol solution in deionized water which contains sodium acetate (100 mM) and tetrabutyl ammonium hydroxide (4 mM). pH of the mobile phase was adjusted 4.5 by the addition of acetic acid. Detection limits for TP, 1-MU, and 1,3-DMU in plasma were 0.2, 0.1 and $0.1\;{\mu}/ml$, respectively and the corresponding values in urine were all $5\;{\mu}g/ml$. Inter- and intra-day variability of the assay for all compounds in the plasma samples was less than 5.5 and 3.8%, respectively. The retention times for 1-MU, 1,3-DMU, and TP were approximately 7, 8.5 and 18 min, respectively. Sample preparation procedure used in this method was simple, rapid and reproducible. Renal clearance of TP and its metabolites in rats showed plasma concentration dependency indicating renal tubular secretion and reabsorption of them.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.533-540
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• 2023

Sweroside is a natural monoterpene derived from Swertia pseudochinensis Hara. Recently, studies have shown that sweroside exhibits a variety of biological activities, such as anti-inflammatory, antioxidant, and hypoglycemic effects. However, its role and mechanisms in high glucose (HG)-induced renal injury remain unclear. Herein, we established a renal injury model in vitro by inducing human renal tubular epithelial cell (HK-2 cells) injury by HG. Then, the effects of sweroside on HK-2 cell activity, inflammation, reactive oxygen species (ROS) production, and epithelial mesenchymal transition (EMT) were observed. As a result, sweroside treatment ameliorated the viability, inhibited the secretion of inflammatory cytokines (TNF-α, IL-1β, and VCAM-1), reduced the generation of ROS, and inhibited EMT in HK-2 cells. Moreover, the protein expression of SIRT1 was increased and the acetylation of p65 NF-kB was decreased in HK-2 cells with sweroside treatment. More importantly, EX527, an inhibitor of SIRT1, that inactivated SIRT1, abolished the improvement effects of sweroside on HK-2 cells. Our findings suggested that sweroside may mitigate HG-caused injury in HK-2 cells by promoting SIRT1-mediated deacetylation of p65 NF-kB.

• The Korean Journal of Physiology
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• v.23 no.2
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• pp.363-375
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• 1989

It has been well known that peripheral infusion of angiotensin II results in an increase of blood pressure, and an elevation of aldosterone secretion, and an inhibition of renin relase. However, the direct effect of angiotensin II on renal function has not been clearly established. In the present study, to investigate the effect of angiotensin II on renal function and renin release, angiotensin II (0.3, 3 and 10 ng/kg/min) was infused into a unilateral renal artery of the unanesthetized rabbit and changes in renal function and active and inactive renin secretion rate (ARSR, IRSR) were measured. In addition, to determine the relationship between the renal effect of angiotensin II and adenosine, the angiotensin II effect was evaluated in the presence of simultaneously infused 8-phenyltheophylline (8-PT, 30 nmole/min), adenosine A 1 receptor antagonist. Angiotensin II infusion at dose less than 10 ng/kg/min decreased urine flow, clearances of para-amino-hippuric acid and creatinine, and urinary excretion of electrolytes in dose-dependent manner. The changes in urine flow and sodium excretion were significantly correlated with the change in renal hemodynamics. Infusion of angiotensin II at 10 ng/kg/min also decreased ARSR, but it has no significant effect on IRSR. The change in ARSR was inversely correlated with the change in IRSR. The plasma concentration of catecholamine was not altered by an intarenal infusion of angiotensin II. In the presence of 8-PT in the infusate, the effect of angiotensin II on renal function was significantly attenuated, but that on renin secretion was not modified. These results suggest that the reduction in urine flow and Na excretion during intrarenal infusion of angiotensin II was not due to direct inhibitions of renal tubular transport systems, but to alterations of renal hemodynamics which may partly be mediated by the adenosine receptor.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.1
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• pp.69-76
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• 1998

Cis-diamminedichloroplatinum II (cisplatin), an effective antitumor agent, induces acute renal failure by unknown mechanisms. To investigate direct toxic effects of cisplatin in the renal proximal tubular transport system, OK cell line was selected as a cell model and $Na^+/H^+$ antiport activity was evaluated during a course of cisplatin treatment. The cells grown to confluence were treated with cisplatin for 1 hour, washed, and incubated for up to 48 hours. At appropriate intervals, cells were examined for $Na^+/H^+$ antiport activity by measuring the recovery of intracellular pH (pHi) after acid loading. Cisplatin of less than 50 ${\mu}M$ induced no significant changes in cell viability in 24 hours, but it decreased the viability markedly after 48 hours. In cells exposed to 50 ${\mu}M$ cisplatin for 24 hours, the $Na^+-dependent$ pHi recovery (i.e., $Na^+/H^+$ antiport) was drastically inhibited with no changes in the $Na^+-independent$ recovery. Kinetic analysis of the $Na^+-dependent$ pHi recovery indicated that the Vmax was reduced, but the apparent Km was not altered. The cellular $Na^+$ and $K^+$ contents determined immediately before the transport measurement appeared to be similar in the control and cisplatin group, thus, the driving force for $Na^+-coupled$ transport was not different. These results indicate that cisplatin exposure impairs the $Na^+/H^+$ antiport capacity in OK cells. It is, therefore, possible that in patients treated with a high dose of cisplatin, proximal tubular mechanism for proton secretion (hence $HCO_3^-$ reabsorption) could be attenuated, leading to a metabolic acidosis (proximal renal tubular acidosis).

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.2
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• pp.107-122
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• 2001

A function of the kidney is elimination of a variety of xenobiotics ingested and wasted endogenous compounds from the body. Organic anion and cation transport systems play important roles to protect the body from harmful substances. The renal proximal tubule is the primary site of carrier-mediated transport from blood into urine. During the last decade, molecular cloning has identified several families of multispecific organic anion and cation transporters, such as organic anion transporter (OAT), organic cation transporter (OCT), and organic anion-transporting polypeptide (oatp). Additional findings also suggested ATP-dependent organic ion transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein (MRP) as efflux pump. The substrate specificity of these transporters is multispecific. These transporters also play an important role as drug transporters. Studies on their functional properties and localization provide information in renal handling of drugs. This review summarizes the latest knowledge on molecular properties and pharmacological significance of renal organic ion transporters.