• 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.

• 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.

• 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.

• 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.

• 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.

• Journal of Ginseng Research
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• v.47 no.6
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• pp.706-713
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• 2023

Background and objective: The ability to inhibit aggregation has been demonstrated with synthetically derived ginsenoside compounds G-Rp (1, 3, and 4) and ginsenosides naturally found in Panax ginseng 20(S)-Rg3, Rg6, F4, and Ro. Among these compounds, Rk3 (G-Rk3) from Panax ginseng needs to be further explored in order to reveal the mechanisms of action during inhibition. Methodology: Our study focused to investigate the action of G-Rk3 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin α_IIbβ₃ using flow cytometry, intracellular calcium mobilization, dense granule secretion, and thromboxane B₂ secretion. In addition, we checked the regulation of phosphorylation on PI3K/MAPK pathway, and thrombin-induced clot retraction was also observed in platelets rich plasma. Key Results: G-Rk3 significantly increased amounts of cyclic adenosine monophosphate (cAMP) and led to significant phosphorylation of cAMP-dependent kinase substrates vasodilator-stimulated phosphoprotein (VASP) and inositol 1,4,5-trisphosphate receptor (IP₃R). In the presence of G-Rk3, dense tubular system Ca²⁺ was inhibited, and platelet activity was lowered by inactivating the integrin αIIb/β₃ and reducing the binding of fibrinogen. Furthermore, the effect of G-Rk3 extended to the inhibition of MAPK and PI3K/Akt phosphorylation resulting in the reduced secretion of intracellular granules and reduced production of TXA₂. Lastly, G-Rk3 inhibited platelet aggregation and thrombus formation via fibrin clot. Conclusions and implications: These results suggest that when dealing with cardiovascular diseases brought upon by faulty aggregation among platelets or through the formation of a thrombus, the G-Rk3 compound can play a role as an effective prophylactic or therapeutic agent.

• 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 Pharmacology
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• v.7 no.1
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• pp.67-76
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• 1971

The excretion of uric acid in man has been of great interest because of its importance as an end product in purine metabolism as well as of its role in causing gout. There are many differences in the modes of renal handling of urate among various species of animals. Uric acid actively secreted by the renal tubules of most vertebrate including amphibians, reptiles, and birds. On the other hand, in most mammals net tubular reabsorption of urate appears to be occurred with some exception, such, as Dalmatian dog. In the rabbits, however, the mechanism of renal excretion of uric acid has long been a subject of controversial results. Within a given group it was possible to find individuals with either net secretion or net reabsorption of urate depend on the experimental conditions. Excretion of urate can be depressed or enhanced by a variety of drugs belonging mainly to the aromatic acid group. Diodrast, probenecid, cinchophen and salicylates have been reported as uricosuric agents, on the other hand, lactate, benzoate, pyrazinoic acid, acetazolamide and chlorothiazide are known to be contraindicated to use for the patient with gout since these agents depress the excretion of uric acid from the kidney. However, complex and sometimes the paradoxical effects on the urate excretion by those above mentioned drugs are not uncommon. The experiments were designed to investigate the mechanisms of renal handling of urate as well as the effects of variety of drugs on the tubular transport of uric acid in the rabbits. Male or female white rabbits, from 1.5 to 2.5 kg in weight, were used. The experimental methods used in these studies were clearance, stop-flow, and retrograde injection techniques. The effects of saline, salicylate, chlorothiazide and probenecid were investigated in each experimental conditions. Results of the experiments were summarized as follows; 1. In the rabbits, the rate of urate clearance was always lower than the rate of inulin clearance. The filtration fraction of the urate was one third on an average, therefore, it is estimated that approximately two thirds of filtered urate was reabsorbed. 2. In the kidneys of rabbits, the urate clearance was increased significantly by administration of chlorothiazide and decreased by probenecid. The administration of salicylate had no effect on the rate of urate clearance. The filtration fraction of urate was increased by chlorothiazide and decreased by probenecid. 3. In the stop-flow studies, the U/P ratio of urate was higher than the U/P ratio of inulin in the proximal region, indicating the secretion of uric acid in the proximal tubules. The proximal peak was increased by chlorothiazide and inhibited by probenecid.4. In the retrograde injection studies, the reabsorption of urate in the proximal region was observed, and these reabsorptive transport of urate was depressed by either probenecid or by chlorothiazide. 5. No distal tubular activity was observed under any of these experimental conditions concerning urate transport. The results of these experiments show that probenecid inhibits both secretory and reabsorptive transport of uric acid in the kidney of the rabbits. The enhancement of secretory transport of urate by chlorothiazide in the clearance study was due to the secondary action of chlorothiazide which inhibits the reabsorptive transport of urate in the proximal tubules. It is evident that the urate transport in the kidneys of rabbits is bidirectional nondiffusive flux both secretory and reabsorptive directions in the proximal tubules.

• 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).