• The Korean Journal of Physiology and Pharmacology
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• 제28권5호
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• pp.413-422
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• 2024

Group I metabotropic glutamate receptors (mGluRs) modulate postsynaptic neuronal excitability and epileptogenesis. We investigated roles of group I mGluRs on low extracellular Mg²⁺ concentration ([Mg²⁺]_o)-induced epileptiform activity and neuronal cell death in the CA1 regions of isolated rat hippocampal slices without the entorhinal cortex using extracellular recording and propidium iodide staining. Exposure to Mg²⁺-free artificial cerebrospinal fluid can induce interictal epileptiform activity in the CA1 regions of rat hippocampal slices. MPEP, a mGluR 5 antagonist, significantly inhibited the spike firing of the low [Mg²⁺]_o-induced epileptiform activity, whereas LY367385, a mGluR1 antagonist, did not. DHPG, a group 1 mGluR agonist, significantly increased the spike firing of the epileptiform activity. U73122, a PLC inhibitor, inhibited the spike firing. Thapsigargin, an ER Ca²⁺-ATPase antagonist, significantly inhibited the spike firing and amplitude of the epileptiform activity. Both the IP₃ receptor antagonist 2-APB and the ryanodine receptor antagonist dantrolene significantly inhibited the spike firing. The PKC inhibitors such as chelerythrine and GF109203X, significantly increased the spike firing. Flufenamic acid, a relatively specific TRPC 1, 4, 5 channel antagonist, significantly inhibited the spike firing, whereas SKF96365, a relatively non-specific TRPC channel antagonist, did not. MPEP significantly decreased low [Mg²⁺]_o DMEM-induced neuronal cell death in the CA1 regions, but LY367385 did not. We suggest that mGluR 5 is involved in low [Mg²⁺]_o-induced interictal epileptiform activity in the CA1 regions of rat hippocampal slices through PLC, release of Ca²⁺ from intracellular stores and PKC and TRPC channels, which could be involved in neuronal cell death.

• 약학회지
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• 제45권4호
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• pp.419-425
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• 2001

The neuronal cell death induced by excess glutamate (Glu) has been implicated in many acute and chronic neurodegenerative diseases including cerebral ischemia. Glu-induced elevation of intra-cellular $Ca^{2+}$ plays a critical role in the excitotoxicity, partly through the activation of a variety of $Ca^{2+}$ dependent enzymes. In the present study, we investigated the Glu-induced modulation of $Ca^{2+}$/calmodulin-dependent protein kinase IV (CaMK IV), a multifunctional enzyme abundantly present in the nuclei of neurons. The exposure of cultured rat cortical neurons to $100{\mu}$M Glu for 3 min dramatically increased CaMK IV activity up to 4.5-fold of the control-treated enzyme activity. The activation was very rapid, reaching peak at 3 min and then declined gradually. Under the same experimental conditions, time-dependent acute and delayed neuronal cell death was observed. Immunoblot analyses using specific antibodies showed that the expressions of CaMK IV and $CaMKK_{\alpha}$ were time-dependently modulated by Glu. Taken together, these results imply that the modulation of CaMK IV activity by Glu may be involved in the cascade of events resulting in neuronal cell death in cortical cultures.

• 대한소아치과학회지
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• 제10권1호
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• pp.139-147
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• 1983

This study was undertaken to evaluate the physiological roles & mechanism of $Ca^{++}$-ATPase & $Mg^{++}$-ATPase in human dental pulp. Each specimen of dental pulp was obtained from the freshly extracted, freeze-dried 242 teeth. $Ca^{++}$-ATPase & $Mg^{++}$-ATPase activity were measured by the release of inorganic phosphate & protein with Spectrophotometer. The results were as follows; 1. The $Ca^{++}$-ATPase & $Mg^{++}$-ATPase activity were significantly increased in developing teeth. 2. The $Ca^{++}$-ATPase & $Mg^{++}$-ATPase activity were significantly decreased in nonvital teeth. 3. The $Ca^{++}$-ATPase & $Mg^{++}$-ATPase activity were significant decreased in deciduous teeth. 4. The $Ca^{++}$-ATPase & $Mg^{++}$-ATPase activity didn't have relation with dental caries. 5. The $Ca^{++}$-ATPase & $Mg^{++}$-ATPase were activated by either $Ca^{++}$ alone or $Mg^{++}$ alone.

• 한국동물학회지
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• 제20권2호
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• pp.101-107
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• 1977

토끼의 골격근 小胞體의 ATPase 活性과 Ca 輸送에 대한 sodium azide, cAMP, G-strophanthin 및 dicumarol의 영향을 측정하였다. Sodium azide(0.05mM)와 G-strophanthin(0.25nM)은 ATPase活性과 Ca 輸送能에 아무런 영향도 미치지 아니하였다. cAMP$(1 \\times 10^-6 M \\sim 5 \\times 10^-4 M)$는 ATPase 活性에는 아무런 영향도 미치지 않았으나 Ca 輸送은 억제하였다. Dicumarol(0.05mM)도 ATPase 活性에는 영향이 없었으나 小胞體의 $8,000 \\sim 12,000 \\times G$分劃에서의 Ca 輸送을 억제하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제3권2호
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• pp.207-213
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• 1999

To examine individual variation in drug metabolism catalyzed by flavin-containing monooxygenase (FMO), 179 Korean volunteers' urinary molar concentration ratio of theobromine (TB) and caffeine (CA) was determined. Their urine was collected for 1 hr (between 4 and 5 hrs) after they drank a cup of coffee containing 115 mg CA and analyzed by an HPLC system. The lowest TB/CA ratio obtained was 0.40, the highest ratio was 15.17 (38-fold difference), and the median ratio for all subjects was 1.87. The mean was 2.66 with 2.36 S.D.. In 134 nonsmokers, the mean ratio was $2.35{\pm}1.93,$ that of 51 males was $2.30{\pm}2.26$ and 83 females was $2.37{\pm}1.85,$ respectively. There was no significant gender difference in the obtained TB/CA ratio (Mann-Whitney test; p=0.518). There were no smokers among the 83 female volunteers. In the remaining 96 male subjects, the ratio obtained in 51 nonsmokers was $2.30{\pm}2.06$ and that of 45 smokers was $3.62{\pm}3.19.$ This indicated that the TB/CA ratio was increased significantly in smokers (p=0.007). However, when the TB/CA ratios (FMO activity) obtained in all 179 Korean volunteers are compared with the urinary concentration ratios of paraxanthine (PX) plus 1,7-dimethylurate (17U) to CA (CYP1A2 activity), there was a weak but significant correlation (Pearson's correlation coefficient test; $r^2=0.28,$ p＜0.0001). This indicates that, although the urinary TB/CA ratio mostly represents FMO activity, minor contribution by CYP1A2 activity cannot be ignored. In conclusion, the FMO activity measured by taking the urinary TB/CA ratio from normal healthy Korean volunteers shows marked individual variations without significant gender differences and the increased TB/CA ratio observed in cigarette smokers may have been caused by the increased CYP1A2 activity.

• 한국식품영양학회지
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• 제9권1호
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• pp.52-58
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• 1996

This study was carried out 19 investigate the characteristics of pectinesterase (PE), polygalacturonase (PG), lipoxygenase(LOX) and peroxidase (POD) in hot pepper to know the effect of hot pepper on food quality during food processing and storage. The results were as follows : 1. The optimum pH of PE was pH 7.5 and the activity of PE below pH 5.5 was revealed scarcely, The concentration of NaCl and $CaCl_2$ that showed the highest activity of PE were 0.2M and 0.05M, respectively. 2. The optimum pH of PG was pH 6.0 and the activity of PG in acidity was higher than that in alkalinity. The activity of PG was maximum at 0.3M NaCl and 0.2mM $CaCl_2$. Above the concentration of 0.5M NaCl and 0.5M $CaCl_2$, the activity of PG was lower than that of PG not adding these salts 3. The optimum pH of LOX was pH 7.0 and pH 8.5. 4. The optimum pH of POD was pH 6.0 and the activity of POD was higher in weak acidity and neutrality than in alkalinity. POD activity was slightly decreased by the increase of NaCl and $CaCl_2$ concentration.

• The Korean Journal of Physiology and Pharmacology
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• 제6권2호
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• pp.109-112
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• 2002

The signal pathways involved in the regulation of AP-1 DNA binding activity in long-term nicotine stimulated bovine adrenal medullary chromaffin (BAMC) cells have not been well characterized. To understand the involvement of second messengers in the regulation of AP-1 DNA binding activity, the present study was designed to define the time-course for inhibition of nicotine-induced responses by cholinergic antagonists, $Ca^{2+}$ and calmodulin (CaM) antagonists, and calcium/calmodulin-dependent protein kinase (CaMK) II inhibitor using electrophoretic mobility shift assay. Nicotine $(10{\mu}M)$ stimulation increased AP-1 DNA binding activity at 24 hr after treatment. Posttreatment with hexamethonium (1 mM) plus atropine $(1{\mu}M)$ (HA), nimodipine $(1{\mu}M),$ or calmidazolium $(1{\mu}M)$ at 0.5, 3, and 6 hr after the nicotine treatment significantly inhibited the AP-1 DNA binding activity increased by long-term nicotine stimulation. However, posttreatment with HA, nimodipine, or calmidazolium at 9 or 12 hr after the nicotine treatment did not affect the nicotine-induced increase of AP-1 DNA binding activity. The pretreatment of BAMC cells with various concentrations of KN-62 inhibited the increase of AP-1 DNA binding activity induced by nicotine in a concentration-dependent manner. KN-62 $(10{\mu}M)$ posttreatment beginning at 0.5, 3, or 6 hr after the nicotine treatment significantly inhibited the increase of AP-1 DNA binding activity. However, KN-62 posttreatment beginning at 9 or 12 hr after the nicotine treatment did not affect the increase of AP-1 DNA binding activity. This study suggested that stimulation (for at least 6 hr) of nicotinic receptors on BAMC cells was necessary for increase of AP-1 DNA binding activity, and activation of $Ca^{2+},$ CaM, and CaMK II up to 6 hr at least seemed to be required for the increase of nicotine-induced AP-1 DNA binding activity.

• 대한의생명과학회지
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• 제18권3호
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• pp.218-226
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• 2012

Dopamine is an enteric neurotransmitter that regulates gastrointestinal motility. This study was done to investigate whether dopamine modulates spontaneous pacemaker activity in cultured interstitial cells of Cajal (ICCs) from mouse using whole cell patch clamp technique, RT-PCR and live $Ca^{2+}$ imaging analysis. ICCs generate pacemaker inward currents at a holding potential of -70 mV and generate pacemaker potentials in current-clamp mode. Dopamine did not change the frequency and amplitude of pacemaker activity in small intestinal ICCs. On the contrary dopamine reduced the frequency and amplitude of pacemaker activity in large intestinal ICCs. RT-PCR analysis revealed that Dopamine2 and 4-receptors are expressed in c-Kit positive ICCs. Dopamine2 and 4 receptor agonists inhibited pacemaker activity in large intestinal ICCs mimicked those of dopamine. Domperidone, dopamine2 receptor antagonist, increased the frequency of pacemaker activity of large intestinal ICCs. In $Ca^{2+}$-imaging, dopamine inhibited spontaneous intracellular $Ca^{2+}$ oscillations of ICCs. These results suggest that dopamine can regulate gastrointestinal motility through modulating pacemaker activity of large intestinal ICCs and dopamine effects on ICCs are mediated by dopamine2 receptor and intracellular $Ca^{2+}$ modulation.

• The Korean Journal of Physiology
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• 제11권2호
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• pp.1-7
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• 1977

The activity of the $Ca^{++}$ activated adenosinetriphosphatase (Ca-ATPase) of actomyosin systeme of rabbit and frog skeletal muscle has been studied at varying pH and temperature. The PH optima of the Ca-ATPase activity of the rabbit actomyosin was rather broad. Over the temperature range of $16-36^{\circ}C$ activity of the enzyme was not appreciably changed between pH 6.4-8.5; below and above which it rapidly reduced. The pH at the inflection point of the enzyme activity increased as temperature decreased, showing the ${\bigtriangleup}pH\;inflection/{\bigtriangleup}T$ of approximately $-0.018\;unit/^{\circ}C$. Consequently, $(OH^-)/(H^+)$ ratio at the inflection point was constant regardless of assay temperature. In the frog actomyosin systems the Ca-ATPase activity was not apparently altered between PH 6.4-7.0 when the incubation temperature was $15{\sim}30^{\circ}C$. Outside of this range of pH, however, the enzyme activity was dramatically decreased. The pH of the inflection point changed inversely with temperature. ${\bigtriangleup}pH\;inflection/{\bigtriangleup}T$ at the acidic side was approximately $-0.018\;unit/^{\circ}C$, whereas that at the alkaline side it was about $-0.037\;unit/^{\circ}C$. The Arrhenius Plot on the Ca-ATPase activity at constant $(OH^-)/(H^+)$ ratio of 1.0 was not linear, but showed break at arround $20^{\circ}C$ for both rabbit and frog actomyosin Preparations. From these results it was speculated that pH dependence of Ca-ATPase activity of rabbit actomyosin systems might reflect titrations of histidine-imidazole and -SH groups, and that of the frog actomyosin represents titrations of histidine-imidazole and lysyllysine ${\alpha}-NH_2$ groups.

• The Korean Journal of Physiology and Pharmacology
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• 제3권2호
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• pp.119-125
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• 1999

Mammalian gastric smooth muscles generate spontaneous rhythmic contractions which are associated with slow oscillatory potentials (slow waves) and spike potentials. Spike potentials are blocked by organic $Ca^{2+}-antagonists,$ indicating that these result from the activation of L-type $Ca^{2+}-channel.$ However, the cellular mechanisms underlying the generation of slow wave remain unclear. Slow waves are insensitive to $Ca^{2+}-antagonists$ but are blocked by metabolic inhibitors or low temperature. Recently it has been suggested that Interstitial Cells of Cajal (ICC) serve as pacemaker cells and a slow wave reflects the coordinated behavior of both ICC and smooth muscle cells. Small segments of circular smooth muscle isolated from antrum of the guinea-pig stomach generated two types of electrical events; irregular small amplitude (1 to 7 mV) of transient depolarization and larger amplitude (20 to 30 mV) of slow depolarization (regenerative potential). Transient depolarization occurred irregularly and membrane depolarization increased their frequency. Regenerative potentials were generated rhythmically and appeared to result from summed transient depolarizations. Spike potentials, sensitive to nifedipine, were generated on the peaks of regenerative potentials. Depolarization of the membrane evoked regenerative potentials with long latencies (1 to 2 s). These potentials had long partial refractory periods (15 to 20 s). They were inhibited by low concentrations of caffeine, perhaps reflecting either depletion of $Ca^{2+}$ from SR or inhibition of InsP3 receptors, by buffering $Ca^{2+}$ to low levels with BAPTA or by depleting $Ca^{2+}$ from SR with CPA. They persisted in the presence of $Ca^{2+}-sensitive$ $Cl^--channel$ blockers, niflumic acid and DIDS or $Co^{2+},$ a non selective $Ca^{2+}-channel$ blocker. These results suggest that spontaneous activity of gastric smooth muscle results from $Ca^{2+}$ release from SR, followed by activation of $Ca^{2+}-dependent$ ion channels other than $Cl^-$ channels, with the release of $Ca^{2+}$ from SR being triggered by membrane depolarization.