• The Korean Journal of Physiology and Pharmacology
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• 제2권1호
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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).

• 대한약리학회지
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• 제13권2호
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• pp.35-39
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• 1977

Cyclic adenosine monophosphate (cAMP), known as a versatile regulator of cellular processes and as a secondary messenger of various hormones and other biogenic agents, such as prostaglandins and histamine, induced prompt and transient antidiuresis followed by mild natriuresis and diuresis, when it was administered into the lateral ventricle of the rabbit in doses ranging from $100\;{\mu}g$ to 1 mg. The initial antidiuresis was brought about by the systemic hypotension, whereas the secondary diuresis seemed to be resulted from the decreased tubular reabsorption of sodium, suggestive of participation of certain endogenous natriuretic agent. This observation suggests that cAMP might be involved in the center-mediated renal action of prostaglandins.

• 대한수의학회지
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• 제35권4호
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• pp.729-733
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• 1995

This study was carried out to determine the effect of renal ischemia on renal function and excretion of amino acid in rabbit. The animal models of renal ischemia induced experimentally by clamping the renal artery for different lengths of time. These results were summarized as follows: 1. Ischemia for 30 or 60 min produced a polyuria which is accompanied by an increase in $Na^+$ excretion. Glomerular filtration rate (GFR) and p-aminohippurate plasma($C_{PAH}$) were not altered by 30 min of ischemia, indicating that transient ischemia results in a marked tubular dysfuction before a reduction in GFR or renal blood flow. 2. Reabsorption of glucose and amino acids such as alanine and lysine was markedly reduced after 30 min of ischemia, and the effect was more pronounced after 60 min of ischemia.

• 대한약리학회지
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• 제2권1호
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• pp.5-12
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• 1966

In this study the influence of Bradykinin, a biogenic polypeptide, on the excretory function of the dog kidney was investigated, utilizing the clearance and stop-flow method. The results are summarized as follows; 1) Bradykinin administered intravenously elicited a marked antidiuresis. 2) When given into the renal artery, however, prompt increase of the urine flow, sodium excretion and free water clearance without significant change in the glomerular filtration rate ensued. 3) It was also effective during an osmotic diuresis with 10% Mannitol infusion, though the response was not so marked. 4) The stop-flow experiment showed that sodium reabsorption in the proximal tubules is inhibited by the infusion of bradykinin into the renal artery. It was thus concluded that the diuretic effect of bradykinin given intra-arterially results from the inhibition of sodium transport in the proximal tubules.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.99.3-100
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• 2003

It is desirable to improve the tumor targeting and blood clearance pharmacokinetics of radiolabeled monoclonal antibodies. To achieve this goal, several avidin-biotin (Bt) binding systems have been developed to decouple large molecular weight antibodies from small radiolabels, thereby achieving high tumor-to-background radioactivity ratios. We inserted a readily catabolizable linker, triglycine (TG), between 3-［/sup125/I］iodobenzoate and dendrimer (G3). We also neutralized the positive charges of G3 by acylation with tetrafluorophenyl glycolate, thereby blocking proximal tubular reabsorption of G3 mediated by charge attraction. (omitted)

• Asian-Australasian Journal of Animal Sciences
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• 제8권3호
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• pp.275-280
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• 1995

The effect of supplemented high protein diet intake on renal urea regulation in swamp buffalo was carried out in the present experiment Five swamp buffalo heifers weighing between 208-284 kg were used for this study. The animals were fed with a supplementary high protein diet and renal function and kinetic parameters for urea excretion were measured. This was compared to a control period where the same animals had been fed only with paragrass and water hyacinth. For 2 months the same animals were fed a mixed of paragrass, water hyacinth plus 2 kgs of a high protein supplement (protein 18.2% DM basis) per head per day. In comparison to the control period, there were no differences in the rate of urine flow, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), plasma urea concentration and filtered urea. In animals supplemented with high protein intake mean values of urea clearance, excretion rate and the urea urine/plasma concentration ratio markedly increased (p < 0.05) while renal urea reabsorption significantly decreased from 40% to 26% of the quantity filtered. In this same study group urea space distribution and urea pool size increased which coincided with an increase in plasma volume (p < 0.05). Plasma protein decreased while plasma osmolarity increased (p < 0.05). Both urea turnover rate and biological half-life of $^{14}C$-urea were not affected by a supplementary high protein intake. The results suggest that animals supplemented with high protein diets are in a state of dynamic equilibrium of urea which is well balanced between urea excreted into the urine and the amount synthesized. The limitation for renal tubular urea reabsorption would be a change in extra-renal factors with an elevation of the total pool size of nitrogenous substance.

• 대한약리학회지
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• 제12권2호
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• pp.43-49
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• 1976

The facts that $PGE_2$ produced diuresis in the rabbit when given into a lateral ventricle of the brain and that $PGF_{2{\alpha}}$ is abundantly found in the brain prompted us to investigate the effects of $PGF_{2{\alpha}}$ introduced directly into the ventricle on the renal function. $PGF_{2{\alpha}}$ given intraventriculary in doses of $10{\mu}g\;and\;100{\mu}g$ elicited prompt diuresis, 10-fold increase of sodium excretion and two-fold increment of potassium excretion. Free water reabsorption also increased along with the increased osmolar clearance. Neither renal plasma flow nor glomerular filtration rate did change significantly. This, along with the fact that the percentage of reabsorbed sodium filtered decreased from 99.5 to 93.9, indicates the tubular site of the diuretic and natriuretic action. Atropine pretreatment did not influence the renal effects of intraventricular $PGF_{2{\alpha}}$. Intravenously administered $PGF_{2{\alpha}}$ in doses of 30 to $100{\mu}g$ did not produce any significant change in renal function. Intraventricular $PGF_{2{\alpha}}$ had no effect on the systemic blood pressure, whereas intravenous administration brought about a transient hypotension. These observations suggest that $PGF_{2{\alpha}}$ induces diuresis and natriuresis via central mechanism, that the site of the action resides in renal tubules, and that the reabsorption of sodium is inhibited in the proximal tubule, possibly through mediation of certain humoral agent. Overall, it is suggested that $PGF_{2{\alpha}}$ might play a roll in regulating renal function through the center.

• Journal of Acupuncture Research
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• 제19권5호
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• pp.199-208
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• 2002

Objective : This study was undertaken to determine if Carthami Semen Aquacupunc- ture(CSA) exerts protective effect against alterations in membrane transport function rabbits with mercury chloride(HG)-induced acute renal failure. Methods : The administration of Hg at a subcutaneous single dose of 10 mg/kg caused a reduction in GFR and an increase in fractional Na excretion, indicating generation of acute renal failure. When CSA were given for 7 days prior to Hg administration, such changes were significantly attenuated. The fractional excretion of glucose and phosphate was increased in rabbits treated with Hg alone. Results : The increase in rabbits treated with Hg following CSA are significantly lower than that in animals treated with Hg alone. Uptakes of glucose and phosphate in purified isolated brush-border membrane and Na-K-ATPase activity in microsomal fraction were inhibited in rabbits treated with Hg alone. Such changes were prevented by CSA. Uptakes of organic ions, PAH and TEA, in renal cortical slices were inhibited by the administration of Hg, which was prevented by CSA. Exposure of renal cortical slices to Hg in vitro caused an increased LDH release and lipid peroxidation, which was significantly prevented by CSA extract. Conclusions : These results indicate that the administration of Hg causes impairment in reabsorption of solutes in the proximal tubule via the generation of reactive oxygen species. CSA provides the protection against the impairment in proximal reabsorption, and its effect may be resulted from its antioxidant effect.

• Applied Microscopy
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• 제18권2호
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• pp.153-166
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• 1988

The fine structure of the salivary glands of the pine moth, Dendrolimus spectabilis Butler, at the last larval period is observed using light and electron microscopes. The moths have single paired tubular salivary glands which openings are connected to the oral cavity through the upper jaw. By the external morphology and its functions, the glands are subdivided into three regions which are anterior reabsorptive region, middle storage region and posterior secretory region. Along the inner canal of the salivary gland two columns of the large glandular cells are connected each other and oriented to ring-like forms. By this cellular orientation, the glands have long and large tubular structure. From anterior to posterior region large nuclei of the glands are ramified like twigs of the tree, and in the cytoplasm of the cell numerous mitochondria and vacuoles are seen. Moreover, basal plasma membranes of the gland cells are heavily infolded. The anterior region of the glands keeps several characteristics related to the reabsorption of the material from the inner cavity to the glandular cells whereas, main salivary material is synthesized and secreted through the long and convoluted posterior region. The apical plasma membranes of the cells are the most heavily invaginated at the posterior regoin, but trachea and tracheoles are distributed only at the middle and posterior regions. In the cytoplasm of the middle region Golgi complexes appeared at the vicinity of the vesicles, and at the posterior region of the salivary glands multivesicular bodies are also observed.

• Journal of Pharmaceutical Investigation
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• 제21권1호
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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.