• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.601-609
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• 1998

The present study was undertaken to examine the role of phospholipase $A_2\;(PLA_2)$ in oxidant-induced inhibition of phosphate transport in primary cultured rabbit renal proximal tubule cells. Uptakes of phosphate and glucose were dose-dependently inhibited by an oxidant t-butylhydroperoxide (tBHP), and the significant inhibition appeared at 0.025 mM of tBHP, whereas tBHP-induced alterations in lipid peroxidation and cell viability were seen at 0.5 mM. tBHP stimulated arachidonic acid (AA) release in a dose-dependent fashion. A $PLA_2$ inhibitor mepacrine prevented tBHP-induced AA release, but it did not alter the inhibition of phosphate uptake and the decrease in cell viability induced by tBHP. tBHP-induced inhibition of phosphate transport was not affected by a PKC inhibitor, staurosporine. tBHP at 0.1 mM did not produce the inhibition of $Na^+-K^+-ATPase$ activity in microsomal fraction, although it significantly inhibited at 1.0 mM. These results suggest that tBHP can inhibit phosphate uptake through a mechanism independent of $PLA_2$ activation, irreversible cell injury, and lipid peroxidation in primary cultured rabbit renal proximal tubular cells.

• Natural Product Sciences
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• v.19 no.4
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• pp.290-296
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• 2013

In preliminary tests, we examined the effect of several fractions isolated from fermented pine needle extract on pacemaker potentials in cultured interstitial cells of Cajal (ICCs) from the mouse colon using a whole cell patch clamp technique. Among these fractions, Fraction 3 (F3) elicited the most powerful depolarization of membrane. Therefore, the aim of the present study was to investigate the effect of F3 obtained from fermented extract of Pinus densiflora needle on pacemaker potentials in ICCs and to establish its mechanism of action. Colonic ICCs generated spontaneous periodic pacemaker potentials in the current-clamp mode. F3 depolarized the membrane and decreased the frequency and amplitude of pacemaker potentials in a dose-dependent fashion. The F3-induced effects on pacemaker potentials were blocked by methoctramine, a muscarinic $M_2$ receptor antagonist, and by glycopyrrolate, a muscarinic $M_3$ receptor antagonist. The F3-induced effects on pacemaker potentials were blocked by external $Na^+$-free solution and by flufenamic acid, a non-selective cation channel blocker, as well as by the removal of external $Ca^{2+}$ and in the presence of thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum. Taken together, these results suggest that F3 of pine needle extract modulates the pacemaker activity of colonic ICCs by the activation of non-selective cation channels via muscarinic $M_2$ and $M_3$ receptors. And external $Ca^{2+}$ influx and intracellular $Ca^{2+}$ release are involved in F3 actions on ICCs.

• Microbiology and Biotechnology Letters
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• v.33 no.3
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• pp.189-193
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• 2005

IgE-dependent histamine-releasing factor(HRF) was initially described as a secretagogue for secretion of histamine from IgE+ basophils from a subset of allergic donors. Previously, we identified that S98 residue of HRF was phosphorylated using anti-HRFpS98 antibody which specifically recognizes the phosphorylated serine residue of HRF and HRFS98A mutant construct. In vitro kinase assay, only wild type HRF was phosphorylated by PKC, and S98A HRF was not affected by PKC. In this study, we attempted to characterize the phosphatase which specifically dephosphorylates HRF by immunoprecipitation and pull-down assay. In RBL-2H3 cells, HRF interacted only with calcineurin (also called as PP2B, calcium/calmodulin-dependent phosphatase) but not with PP1 or PP2A. The results suggest that HRF is most likely dephosphory-lated by calcineurin.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.4
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• pp.319-324
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• 2000

The causal relationship between heat shock protein (HSP) and second window of cardioprotective effect is still undetermined. In the present study, we assessed whether HSP-producing substances, amphetamine and ketamine, afforded protection against reperfusion-induced ventricular fibrillation (VF) and these protective effect remained after the inhibition of HSP72 production by quercetin, a mitochondrial ATPase inhibitor. Adult mongreal male cats $(n=60,\;2.5{\sim}4\;kg)$ were used in this study. Experimental animals were divided into five groups; control group (n=15), amphetamine ('A', n=11) group, ketamine ('K', n=9) group, amphetamine-ketamine ('AK', n=16) group and amphetamine-ketamine-quercetin ('AKQ', n=9) group. Twenty-four hours after the drug treatment, an episode of 20-min coronary artery occlusion was followed by 10-min reperfusion. The incidence of reperfusion-induced VF in the AK and AKQ groups was significantly lower than that in control group (p＜0.01). After the ischemia/reperfusion procedure, western blot analysis of HSP72 expression in the myocardial tissues resected from each group was performed. HSP72 production in the AK group was marked, whereas HSP72 was not detected in the AKQ and control groups. These results suggest that the suppressive effect against reperfusion-induced VF induced by amphetamine and ketamine is not mediated by myocardial HSP72 production but by other mechanisms.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.6
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• pp.865-871
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• 2006

Signs of dental discolouration, difficulty in mastication, bony exostosis and debility were observed in cattle from Qingtongxia Ningxia, China where fluoride concentration in drinking water, soil, fodder, serum, bone, teeth, haircoat and urine were significantly higher than the corresponding health site. The problem of fluorosis in beef cattle is attributable to water containing toxic levels of fluoride. The objective of this paper was therefore to evaluate the influence of fluoride on erythrocyte parameters in cattle under high fluoride and low selenium conditions, as well as the protective efficacy of selenium exposure in feedstuff for bovine endemic fluorosis. Sixteen 6 to 7 year-old high fluoride beef cattle were randomly allotted into two groups each with eight cows: high fluoride control group, and supplemented with 0.25 mg/kg selenium per day for 83 days respectively. In addition, eight 6 to 7 year-old normal control beef cattle were selected from a non-high fluoride site. Blood samples were collected on day 0, 30 and 83 for erythrocyte parameters analysis and scanning electronic microscopy. The results indicated that erythrocytes, hemoglobin, packed cell volume values and $Na^+-K^+$ ATPase activity from affected cattle on the high fluoride site were significantly reduced during the period as compared with the corresponding samples of normal control cattle, a great number of echinocytes were present in peripheral blood, and subsequent anaemia. However, affected cattle exposed to selenium revealed increasable erythrocyte parameters, the extent of elevation in these values being dependent on the duration of supplementation with selenium. These findings suggest that fluoride exposure can cause erythrocyte damage, whereas selenium supplementation can antagonize fluoride-induced generation of free radicals and cumulative effects of lipid peroxidation in erythrocytes. Selenium supplementation may help to alleviate the possible hazards associated with bovine endemic fluorosis.

• Korean Journal of Acupuncture
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• v.17 no.1
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• pp.179-190
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• 2000

This study was undertaken to determine whether Juglandis semen extract solution (JLS solution) exerts protective effect against oxidant-induced inhibition of glutamate uptake by synaptosomes. Synaptosome was prepared from rabbit brain cortex. Glutamate uptake increased by incubation time during 10 minutes, which was significantly inhibited by 1mM t-buthylhydroperoxide(t-BHP). JLS solution prevented t-BHP-induced inhibition of glutamate uptake in a dose-dependent manner. t-BHP reduced glutamate uptake in dose-dependent fashion, which was significantly prevented by 2% JLS solution. t-BHP(1mM) and $ascorbate/Fe^{2+}(50/1{\mu}M)$ increased lipid peroxidation in synaptosomes by 5-fold, and it was significantly prevented by 2% JLS solution. $HgCl_2(0.1mM)$ inhibited glutamate uptake and increased lipid peroxidation. These changes were prevented by 2% JLS solution. Synaptosomal Na-K-ATPase activity was inhibited by t-BHP(1mM) and $H_2O_2(50mM)$, which was prevented by 2% JLS solution. The results indicate that JLS solution prevents oxidant-induced inhibition of glutamate by synaptosomes, and this may result from inhibition of lipid peroxidation induced by oxidants.

• Korean Journal of Acupuncture
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• v.23 no.1
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• pp.45-57
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• 2006

Objective : This study was undertaker to determine if Juglandis Semen herbal acupuncture (JSA) exerts protective effect against alterations in membrane transport function in rabbits with mercury-induced acute renal failure. Methods : Nephrotoxicity was induced by subcutaneous administration of Hg(a single dose of 10mg/kg) and JSA was performed at both sides of Shenshu($(BL_{23})$, Sinsu) for 7 days. Results: The administration of Hg at a subcutaneous single dose of 10 mg/kg caused a reduction in GFR to 12% of the basal value and an increase in fractional $Na^+$ excretion to 8.9-fold, indicating generation of acute renal failure. When JSA were given for 7 days prior to Hg administration, such changes were significantly attenuated. The fractional excretion of glucose and phosphate was increased to approximately 102- and 35-fold, respectively, in rabbits treated with Hg alone. The increase in rabbits treated with Hg following ISA 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, suggesting that impairment in proximal reabsorption of glucose and phosphate is resulted from a direct damage of membrane transport carriers and disruption of the normal $Na^+$ gradient. Such changes were prevented by JSA. Conclusion 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. JSA provides the protection against the Hg-induced impairment in proximal reabsorption, and its effect may be resulted from its antioxidant action.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.12
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• pp.1897-1906
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• 2019

Objective: An experiment was conducted to investigate the effects of dietary non-phytate phosphorus (nPP) deficiency on intestinal pH value, digestive enzyme activity, morphology, nutrient utilization, and gene expression of NaPi-IIb in meat ducks from 1 to 21 d of age. Methods: A total of 525 one-d-old Cherry Valley ducklings were fed diets (with 7 pens of 15 ducklings, or 105 total ducklings, on each diet) with five levels of nPP (0.22%, 0.34%, 0.40%, 0.46%, or 0.58%) for 21 d in a completely randomized design. Five experimental diets contained a constant calcium (Ca) content of approximately 0.9%. Body weight (BW), body weight gain (BWG), feed intake (FI), and feed to gain ratio (F:G) were measured at 14 and 21 d of age. Ducks were sampled for duodenum and jejunum digestion and absorption function on 14 and 21 d. Nutrient utilization was assessed using 25- to 27-d-old ducks. Results: The results showed ducks fed 0.22% nPP had lower (p<0.05) growth performance and nutrient utilization and higher (p<0.05) serum Ca content and alkaline phosphatase (ALP) activity. When dietary nPP levels were increased, BW (d 14 and 21), BWG and FI (all intervals), and the serum phosphorus (P) content linearly and quadratically increased (p<0.05); and the jejunal pH value (d 14), duodenal muscle layer thickness (d 14), excreta dry matter, crude protein, energy, Ca and total P utilization linearly increased (p<0.05); however, the serum ALP activity, jejunal $Na^+-K^+$-ATPase activity, and duodenal NaPi-IIb mRNA level (d 21) linearly decreased (p<0.05). Conclusion: The results indicated that ducks aged from 1 to 21 d fed diets with 0.22% nPP had poor growth performance related to poor intestinal digestion and absorption ability; but when fed diets with 0.40%, 0.46%, and 0.58% nPP, ducks presented a better growth performance, intestinal digestion and absorption function.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.517-526
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• 2009

The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC $(20\sim180\;{\mu}g/ml)$ perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC $(60\;{\mu}g/ml)$, the CA secretory responses to veratridine (a selective $Na^+$ channel activator $(10\;{\mu}M)$, Bay-K-8644 (a L-type dihydropyridine $Ca^{2+}$ channel activator, $10\;{\mu}M$), and cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, $10\;{\mu}M$) were significantly reduced, respectively. In the simultaneous presence of PCRC $(60\;{\mu}g/ml)$ and L-NAME (an inhibitor of NO synthase, $30\;{\mu}M$), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high $K^+$, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC $(60\;{\mu}g/ml)$ was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of $Ca^{2+}$ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.9-14
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• 2016

Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the $Na^+-K^+$-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain ($3.0{\mu}mol/L$) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 ($3.0{\mu}mol/L$), an inhibitor for reverse mode of $Na^+-Ca^{2+}$ exchangers (NCX), but did not by L-type $Ca^{2+}$ channel blocker nifedipine ($1.0{\mu}mol/L$) or protein kinase A (PKA) selective inhibitor H-89 ($3.0{\mu}mol/L$). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline ($100.0{\mu}mol/L$), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP ($0.5{\mu}mol/L$) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 ($30{\mu}mol/L$), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.