• Biomolecules & Therapeutics
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• 제1권2호
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• pp.171-176
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• 1993

Purpose of the present study was to clarify the role of noradrenergic neural activities in hypothalamus for either triggering or maintaining hypertension in deoxycorticosterone (DOCA)-salt hypertensive rats. Two groups of animals were prepared: 1) normotensive Wistar rats and 2) DOCA-salt induced hypertensive rats. Voltage dependent $^{45}Ca^{++}$ uptake, endogenous norepinephrine release, and the catecholamine content in the hypothalamus of DOCA-salt hypertensive and normotensive Wistar rats were compared. Animals at 4, 6 and 16 week-old of two groups were sacrificed by decapitation and hypothalamus was dissected out. Voltage dependent calcium uptake and norepinephrine release were determined from hypothalamic synaptosomes either in low potassium or high potassium stimulatory condition by using $^{45}Ca^{++}$ isotope and HPLC-ECD technique. Degrees of voltage dependent $^{45}Ca^{++}$ uptake and norepinephrine release in hypothalamic synaptosomes of 16-week-old DOCA-salt hypertensive rats were significantly greater than those of age matched normotensive control rats. The norepinephrine and dopamine contents of hypothalamus were about the same in two groups of animals. These results suggest that the alteration of evoked norepinephrine release related to calcium uptake in hypothalamus may play a role in the maintenance of hypertension in DOCA-salt hypertensive rats.

• 약학회지
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• 제44권6호
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• pp.499-504
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• 2000

We previously demonstrated that 6-paradol, a compound structurally related to capsaicin, showed to produce prolonged analgesia in experimental animals. The effects of 6-paradol on the release of adenosine were investigated in the rat spinal cord synaptosomes by high performance liquid chromatography. In the presence of $Ca^{++}$, adenosine was released from synaptosomes of rat spinal cord by 6-paradol and capsaicin in a dose dependent manner. Nifedifine, L-type voltage sensitive calcium channel blocker, was found to be ineffective in releasing adenosine by $10\;{\mu}M$ 6-paradol. After exposure to $10\;{\mu}M$ capsazepine, a novel capsaicin selective antagonist, the level of adenosine evoked by $10\;{\mu}M$ 6-paradol was decreased by 75%, and that evoked by $10\;{\mu}M$ capsaicin was blocked completely. These results suggest that the analgesic effect of 6-paradol might be mediated by the vanilloid (capsaicin) sensitive pathway, or the direct binding to the vanilloid receptor.

• The Korean Journal of Physiology and Pharmacology
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• 제1권4호
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• pp.367-376
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• 1997

The effect of an organic peroxide, t-butylhydroperoxide (t-BHP), on glutamate uptake was studied in synaptosomes prepared from cerebral cortex. t-BHP inhibited the $Na^+-dependent$ glutamate uptake with no change in the $Na^+-independent$ uptake. This effect of t-BHP was not altered by addition of $Ca^{2+}$ channel blockers (verapamil, diltiazem and nifedipine) or $PLA_2$ inhibitors (dibucaine, butacaine and quinacrine). However, the effect was prevented by iron chelators (deferoxamine and phenanthroline) and phenolic antioxidants (N,N'-diphenyl-phenylenediamine, butylated hydroxyanisole, and butylated hydroxytoluene). At low concentrations (＜1.0 mM), t-BHP inhibited glutamate uptake without altering lipid peroxidation. Moreover, a large increase in lipid peroxidation by $ascorbate/Fe^{2+}$ was not accompanied by an inhibition of glutamate uptake. The impairment of glutamate uptake by t-BHP was not intimately related to the change in $Na^+-K+-ATPase$ activity. These results suggest that inhibition of glutamate uptake by t-BHP is not totally mediated by peroxidation of membrane lipid, but is associated with direct interactions of glutamate transport proteins with t-BHP metabolites. The $Ca^{2+}$ influx through $Ca^{2+}$ channel or $PLA_2$ activation may not be involved in the t-BHP inhibition of glutamate transport.

• The Korean Journal of Physiology and Pharmacology
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• 제6권2호
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• pp.87-91
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• 2002

The aim of this study was to investigate the role of $Ca^{2+}-channel$ blockers in norepinephrine (NE) release from rat hippocampus. Slices and synaptosomes were incubated with $[^3H]-NE$ and the releases of the labelled products were evoked by 25 mM KCl stimulation. Nifedipine, diltiazem, nicardipine, flunarizine and pimozide did not affect the evoked and basal release of NE in the slice. But, diltiazem, nicardipine and flunarizine decreased the evoked NE release with a dose-related manner without any change of the basal release from synaptosomes. Also, a large dose of pimozide produced modest decrement of NE release. ${\omega}-conotoxin$ (CTx) GVIA decreased the evoked NE release in a dose-dependent manner without changing the basal release. And ${\omega}-CTxMVIIC$ decreased the evoked NE release in the synaoptosomes without any effect in the slice, but the effect of decrement was far less than that of ${\omega}-CTxGVIA.$ In interaction experiments with ${\omega}-CTxGVIA,\;{\omega}-CTxMVIIC$ slightly potentiated the effect of ${\omega}-CTxGVIA$ on NE release in the slice and synaptosomal preparations. These results suggest that the NE release in the rat hippocampus is mediated mainly by N-type $Ca^{2+}-channels,$ and that other types such as L-, T- and/or P/Q-type $Ca^{2+}-channels$ could also be participate in this process.

• 대한한방내과학회지
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• 제19권1호
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• pp.431-441
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• 1998

This study was undertaken to determine whether Buthus exract(BTE) affects Na^+-K^+-ATPase$ activity of nervous tissues. The enzym activity was measured in synaptosomal fraction prepared from rabbit brain cortex. Na^+-K^+-ATPase$ activity was inhibited by BTE over concentration range of 0.05-0.5% in a dose-dependent manner. The enzyme activity was increased by an increase in $Na^+$ concentration from 5 to 100mM, $K^+$ concentration from 0.5 to 10mM, and $Mg^{2+}$ concentration from 0.2 to 5mM. These changes in ion concentrations did not produce any effect on the inhibitory effect of BTE on $Na^+-K^+-ATPase$ activity. An increase in ATP concentration from 0.1 to 3mM caused an increase in the enzyme activity. The inhibition of the enzyme activity by BTE were not different between two ATP concentrations. A sulfhydryl group protector DTT prevented PCMB-induced inhibition of $Na^+-K^+-ATPase$ activity, but the BTE-induced inhibition was not altered by DTT. The inhibition of enzyme activity by combination of ouabain and BTE was not different from that by Buthus alone. These results suggest that Buthus exerts inhibitory effect on $Na^+-K^+-ATPase$ activity in cerebral synaptosomes, and the action mechansim is similar to that of ouabain.

• Applied Microscopy
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• 제17권2호
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• pp.41-54
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• 1987

This experiment was performed to investigate the acute and chronic effects of lead on cerebral cortex. In acute treatment, mouse were injected with lead acetate at dose of 0.3 mmole/kg body weight, and in chronic treatment, mouse were supplied 0.03 M lead acetate sol. in the place of water. After treatment, mouse were sacrificed at time intervals of 24, 48, 72, and 96 hours in acute treatment and at time intervals of 4 weeks and 8 weeks in chronic treatment. In acute treatment, acetylcholinesterase activity is reduced at 72 hours and recovered at 96 hours in homogenate, and reduced at 24 hours and recovered at 72 hours in crude synaptosomes. In chronic treatment, acetylcholinesterase activity is increased in young mouse but reduced in mother mouse. Ultrastructural changes were composed of swelling of Golgi apparatus, nerve terminals with diminished synaptic vesicles, and vacuolated myeline lamellae of myelinated axon.

• Applied Microscopy
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• 제32권2호
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• pp.131-147
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• 2002

살오징어와 서해낙지의 시엽은 피질부와 수질부로 크게 나눌 수 있었고, 피질부는 3층(외과립세포층, 망상층, 그리고 내과립세포층)으로 구성되어 있었다. 피질부의 두께는 오징어에서 약 $420{\sim}450{\mu}m$ (외과립층, $100{\mu}m$; 망상층, $170{\sim}200{\mu}m$ 그리고 내과립층, $150{\mu}m$) 정도였고 낙지인 경우는 약 $250{\sim}290{\mu}m$ (외과립세포층, $50{\sim}70{\mu}m$; 망상층, $100{\sim}120{\mu}m$; 내과립세포층, $100{\mu}m$) 정도로 관찰되어 오징어가 낙지에 비해 $170{\mu}m$ 정도 더 두터웠다. 살오징어의 외과립세포층에서는 3종류의 신경세포(A형, B형 그리고 C형)와 이들을 감싸거나 인접되어 있는 신경교세포들이 관찰되었고, 서해낙지에서는 2종류의 신경세포(A형과 B형)와 1종류의 신경교세포가 관찰되었다. 망상층에는 전연접자루와 신경말단들이 서로 연접되어 다양한 형태의 연접체를 형성하였는데, 살오징어에서는 전자밀도가 높은 소포, 과립소포, 그리고 투명소포 등이 혼재되어 있거나 한 종류만을 포함하는 경우 등 다양한 반면, 서해낙지에서는 투명소포만을 소지한 경우와 과립소포만을 소지한 경우, 그리고 투명소포와 과립소포들이 혼합된 경우 등 3종류의 연접체가 주로 관찰되었다. 내과립세포층은 구조적으로 두 종에서 거의 비슷한 형태이며 2종류의 신경세포(A형과 B형)와 1종류의 신경교세포로 구성되어 있었다. 살오징어의 수질부에서는 크기가 $7{\times}5{\mu}m$ 정도인 세포들이 일렬로 배열되어 있어 울타리세포층을 형성하였으나 서해낙지에서는 이들이 관찰되지 않았다.

• 대한약리학회지
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• 제24권1호
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• pp.17-29
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• 1988

Lidocaine 투여에 의한 전신경련의 작용기전을 추구하고자 흰쥐의 전체뇌를 또는 선조체, 해마, 및 중뇌를 부위별로 적출하여 synaptosomes를 마련하고 $20{\mu}M$ veratrine또는 $5{\mu}M\;K^+$ 첨가에 의한 신경 전달물질 (Aspartic acid, Glutamic acid, GABA, Norepinephrine)의 유리촉진작용에 미치는 lidocaine, propranolol, norepinephrine 또는 serotonin의 억제효과를 관찰하였고 $[^3H]M$와 $[^3H]-glutamic$ acid의 synaptosomes로의 섭취에 미치는 lidocaine의 영향도 관찰하였다. 아울러 crude synaptic membrane을 이용하여 $[^3H]-GABA$와 $[^3H]-glutamic$ acid의 수용체 결합에 미치는 lidocaine의 작용도 실험하여 다음과 같은 결과를 얻었다. 1. Lidocaine과 propranolol은 veratrine에 의한 aspartate, glutamate, GABA 및 norepinephrine의 유리를 억제하였고, 그중 GABA 유리에 대한 억제작용이 가장 현저하였다. 2. Norepinephrine과 serotonin은 $100{\mu}M$의 농도에서 veratrine에 의한 aspartate, glutamate 및 GABA의 유리촉진 작용을 억제하였다. 3. Lidocaine은 veratrine에 의한 아미노산 유리촉진 효과에 대해서 보다 과 $K^+$ 에 의한 유리촉진 효과를 더욱 약하게 억제하였고 특히 GABA 유리에 대한 억제작용이 가장 약했다. 4. GABA와 glutamic acid의 수용체 결합과 synaptosomes로의 섭취는 1 mM 이하의 lidocaine농도에서 크게 면화가 없었다. 이상의 결과로 보아 신경전도물질의 veratrine에 의한 유리가 과 $K^+$에 의한 유리보다 더욱 생리적이라는 점을 고려한다면, lidocaine 경련은 lidocaine이 흥분성 전도물질인 aspartate나glutamate보다 억제성 전도물질인 GABA의 유리를 더욱 현저하게 억제함으로서 나타남을 시사한다.

• 대한약리학회지
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• 제24권2호
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• pp.179-187
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• 1988

소듐에 의한 칼슘의 유리는 verapamil, TTX, TEA의 영향을 받지 않았다. $100\;{\mu}M\;Cd6{++}$과 $Zn^{++}$은 소듐에 의한 칼슘 유출을 유의하게 억제하였다. $Cd^{++}$은 $Ki\;100\;{\mu}M\;Cd6{++}$로써 비상경적으로 소듐-칼슘 교환이동을 억제하였다. $Cd^{++}$은 SH기의 산화를 초래하였으나, $Zn^{++}$은 거의 영향을 나타내지 않았다. $Cd^{++}$과 $Zn^{++}$은 $Na^+-Ca^{++}$ ATPase를 효과적으로 억제하였으나 $Ca^{++}-Mg^{++}$ ATPase를 약간 억제시켰다. Carbonyl cyanide chlorophenylhydrazone, 2,4-dinitrophenol과 sodium arsenate는 소듐에 의한 칼슘 유리를 촉진하였다. Dibucaine과 oligomycin은 소듐에 의한 칼슘의 유리를 약간 억제하였으나, 이에 반하여 ouabain은 약간 촉진하였다. 이상의 실험 결과로부터 신경 세포막에서의 소듐-칼슘 교환은 이온 통로를 통하여 이루어지지 않을 것으로 시사되었다. 소듐-칼슘 교환이동은 $Cd^{++}$에 민감하게 억제되고 이 이동기전에 synaptosome막의 SH기가 관여할 것으로 사료되었다. 또한 소듐-칼슘 교환은 세포막 단백질 성분의 인산화 반응 동안에 억압될 것으로 추정되었다.

• 약학회지
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• 제38권1호
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• pp.57-66
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• 1994

We studied the effect of eicosanoids on the content of energy metabolites and the intrasynaptosomal $Ca^{++}([Ca^{++}]_i)$ concentration in cerebral ischemic rats. An ischemic model was made by bilateral carotid artery ligation (BCAL) and by incubation of synaptosomes under aglycemic and $N_2$ gas bubbling condition. The content of ATP, creatine phosphate and glucose decreased at 15 minutes after BCAL while that of lactate increased in male Wistar rats. Oral administration of EPA(100 mg/ml/Kg/day) or DHA(16 mg/ml/Kg/day) for 6 weeks improved both the decreases and the increase of the cerebral energy metabolites. In addition, the increase of $[Ca^{++}]_i$, under BACL was suppressed by EPA or DHA treatment. When the both Wistar rats and SHR were administered orally with EPA or DHA for 6 weeks, the effect on the increase of $[Ca^{++}]_i$ under ischemia by $N_2$ gas bubbling were protected. From these results, it may be that EPA or DHA treatment were greatly contributed to preservation of ischemic cerebral energy metabolism and $Ca^{++}$ concentration.