• 대한치과의사협회지
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• 제12권6호
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• pp.419-423
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• 1974

The authors have investigated the roles of cortisone and calcium on the depressive effects of local anesthetics on the acetylcholine-induced skeletal muscle contraction in frog. The results are as follows. 1. Tetracaine, cocaine, lidocaine and procaine decreased the acetylcholine-induced skeletal muscle contraction. 2. Cortisone increased the depressive effects of local anesthetics on the acetyl-choline-induced skeletal muscle contraction. 3. There was a tendency that in high calcium concentration, the depressive effects of cocaine and lidocaine on acetylcholine-induced skeletal muscle contraction were increased.

• The Korean Journal of Physiology
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• 제9권2호
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• pp.41-48
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• 1975

The failure of the action potential at the end-plate membrane to reach the sodium equilibrium potential is due to the stimulating action of acetylcholine on $Na^+-K^+$ pump. This action of acetylcholine causes an enormous increase in the $K^+$ transport rate. The quantitative amount of potassium ions in the inside of the end-plate membrane prevented the permeability of sodium ions during the depolarization phase of the action potential. It would favor the changes in the shape of action potential by acetylcholine which are always toward a fixed potential slightly below the zero line. The increased $Na^+-K^+$ pump activity by acetylcholine is responsible for the hypopolarization of membrane. This reduces the membrane resistance of the end-plate during transmitter activity.

• Bulletin of the Korean Chemical Society
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• 제35권10호
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• pp.2911-2916
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• 2014

The gas phase structures, energetics, and interconversion pathways of five lowest energy conformers of acetylcholine were examined employing the B3LYP, MP2, and CCSD(T) methods in conjunction with diverse basis sets including the correlation consistent aug-cc-pVDZ and aug-cc-pVTZ basis sets. It is found that use of adequate basis set containing proper polarization and diffuse functions capable of describing the floppy potential energy surface of acetylcholine is important in correctly predicting the relative stability of these conformers. The interconversion pathways and barrier heights between these conformers were elucidated by examining the potential energy surface for torsional motion, which also manifested the presence of chiral conformations of acetylcholine corresponding to the original conformations. On the basis of high level electronic energy calculations and thermal contribution analysis, four lowest energy conformers appear to be populated in the energy range of less than 1 kcal/mol at room temperature.

• 동국한의학연구소논문집
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• 제4권
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• pp.211-236
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• 1995

This study was carried out to investigate the effects of Mahwangtang and Gamimahwangtang extract and its constituent herbs on the contractile force of rat tracheal smooth muscle treated with acetylcholine and to elucidate its mechanism. The results of this study were follows ; 1. Mahwangtang and Gamimahwangtang significantly inhibited the contractile response of isolated rat tracheal smooth muscle by acetylcholine, and Gamimahwangtang more significantly effects than Mahwangtang. 2. Gamimahwangtang without Ephedrae Herba significantly inhibited the contractile response of isolated rat tracheal smooth muscle by acetylcholine and less inhibited the contractile force than Gamimahwangtang. 3. Gamimahwangtang without Fritillariae Roylei Bulbus, Platycodi Radix, Cinnamomi Ramulus, significantly inhibited the contractile response of isolated rat tracheal smooth muscle by acetylcholine and less inhibited the contractile force than Gamimahwangtang. 4. Gamimahwangtang without Armeniacae Amarum Semen, Glycyrrhizae Radix significantly inhibited the contractile response of isolated rat tracheal smooth muscle by acetylcholine and its difference did not to the Gamimahwangtang. 5. Gamimahwangtang without Ginseng Radix significantly inhibited the contractile response of isolated rat tracheal smooth muscle by acetylcholine and more significantly effects than Gamimahwangtang.

• 약학회지
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• 제39권3호
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• pp.231-242
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• 1995

Electroconvulsive shock (ECS) increases the activity of acetylchohnesterase and decreases in brain acetylcholine levels. A large amount of free fatty acids accumulated in the brain tissue affects cerebral blood flow, brain edema and inflammation and results in brain injury. The present study examined the effect of docosahexaenoic acid (DHA) and D,L-pyroglutamic acid (D,L-PCA) on the learning and memory deficit using the passive avoidance failure technique and on the change of acetylcholine and choline level in the cerebral cortex of ECS-induced mice. The application of ECS (25mA, 0.5sec) induced a significant decrease in memory function for 30 min. ECS-induced a significant decrease in cortical acetylcholine and choline levels 1 min following the ECS application, which were almost recovered to ECS control level after 30 min. DHA (20 mg/kg, i.p.). administered 24 hr before shock. prevented the ECS-induced passive avoidance failure and the decrease of acetylcholine level 1 min following the ECS application. DHA failed to elicit a change in cortical choline level. DHA did not affect memory function and the cortical Ach and choline level of normal mice. The administration of D,L-PCA (500 mg/kg, i.p.) increased the effect of DHA on memory function and the change of cortical acetylcholine level of ECS induced mice. These results suggest that DHA treatment may be contributed to the prevention against memory deficit, and to the activation of cholinergic system in the ECS induced mice.

• The Korean Journal of Physiology and Pharmacology
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• 제15권1호
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• pp.17-22
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• 2011

Quercetin mainly exists in the skin of colored fruits and vegetables as one of flavonoids. Recent studies show that quercetin, like other flavonoids, has diverse pharmacological actions. However, relatively little is known about quercetin effects in the regulations of ligand-gated ion channels. In the previous reports, we have shown that quercetin regulates subsets of homomeric ligand-gated ion channels such as glycine, 5-$HT_{3A}$ and ${\alpha}7$ nicotinic acetylcholine receptors. In the present study, we examined quercetin effects on heteromeric neuronal ${\alpha}3{\beta}4$ nicotinic acetylcholine receptor channel activity expressed in Xenopus oocytes after injection of cRNA encoding bovine neuronal ${\alpha}3$ and ${\beta}4$ subunits. Treatment with acetylcholine elicited an inward peak current ($I_{ACh}$) in oocytes expressing ${\alpha}3{\beta}4$ nicotinic acetylcholine receptor. Co-treatment with quercetin and acetylcholine inhibited $I_{ACh}$ in oocytes expressing ${\alpha}3{\beta}4$ nicotinic acetylcholine receptors. The inhibition of $I_{ACh}$ by quercetin was reversible and concentration-dependent. The half-inhibitory concentration ($IC_{50}$) of quercetin was $14.9{\pm}0.8\;{\mu}M$ in oocytes expressing ${\alpha}3{\beta}4$ nicotinic acetylcholine receptor. The inhibition of $I_{ACh}$ by quercetin was voltage-independent and non-competitive. These results indicate that quercetin might regulate ${\alpha}3{\beta}4$ nicotinic acetylcholine receptor and this regulation might be one of the pharmacological actions of quercetin in nervous systems.

• 동의생리병리학회지
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• 제25권3호
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• pp.406-416
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• 2011

In this study, we have verified the memory and cognitive enhancing effect of Longanae Arillus, the fruit of Euphoria longana Lamarck, which has been used as a tonic and for the treatment of amnesia, insomnia, and palpitations in oriental medicine. To investigate the effect of Longanae Arillus water extract(LAE) on the memory and cognitive dysfunction, scopolamine (1 mg/kg, i.p.) was injected in C57BL/6 mice and several behavior tests including Y-maze, Morris water-maze, passive avoidance and fear conditioning tests were conducted. Administration of LAE (100 or 200 mg/kg/day, p.o.) effectively improved scopolamine-induced memory impairment and dysfunction. To further determine the possible molecule mechanism of LAE, we have examined the activity and/or mRNA expression of diverse proteins involved in the acetylcholine metabolism. LAE particularly increased the amount of acetylcholine in the cortex which was mediated by suppression of acetylcholine esterase (AchE) activity. In addition, LAE elevated the mRNA expression of muscarinic acetylcholine receptors (mAchRs) without affecting the mRNA levels of choline acetyltransferase (ChAT) and acetylcholine esterase (AchE). In another experiment, LAE effectively inhibited mRNA expression of pro-inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-$1{\beta}$ (IL1-${\beta}$), which seemed to be mediated by inhibition of upstream transcription factor NF-${\kappa}B$ and extracellular-regulated kinase 1/2 (ERK1/2). These results demonstrate that Longanae Arillus can increase acetylcholine amount the cortex via regulation of AchE activity as well as mAchRs expression and decrease pro-inflammatory responses via inhibition of NF-${\kappa}B$ signaling pathway, thereby having therapeutic potential to improve memory and cognitive deficit in amnesia.

• 생명과학회지
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• 제28권4호
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• pp.408-414
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• 2018

Actein은 널리 알려진 승마 추출물의 주요 생리 활성 효능 성분이다. 본 연구에서는 acetylcholine 수용체의 활성을 억제하는 것으로 활용된 AchBP 단백질 길항제(antagonist) tubocurarine과 승마 추출물의 효능 성분 actein 및 actein 유도체(27-deoxyactin, (26S)-actein, (26R)-actein)들의 AchBP 단백질 B와 C domain 활성 부위에 대한 친화도 분석 실험을 컴퓨터 분자결합 분석 방법을 통해 비교하였다. AchBP 단백질 B와 C domain의 3차원 구조정보는 PDB database (PDB ID: 2XYT)를 활용하였다. In silico 결합 분석을 수행하기 위해 PyRx, Autodock Vina, Discovery Studio Version 4.5, and NX-QuickPharm 프로그램을 각 분석 조건에 따라 활용하였다. AchBP 단백질 B와 C domain 활성 부위에 대한 actein의 최대 결합친화도는 -10.50 kcal/mol으로 나왔으며 이는 -9.80 kcal/mol으로 분석된 tubocurarine의 결합 친화도 보다 훨씬 더 높고 효율적인 것으로 분석되었다. Tubocurarine에 비하여 결합친화도 값이 높게 분석된actein, 27-deoxyactein, (26R)-actein 유도체 성분들과 상호작용 하는 AchBP 단백질 활성 부위의 아미노산들 가운데 tryptophan 84와 tyrosine 147이 높은 결합친화도를 형성하는데 매우 중요한 역할을 하는 아미노산으로 예상이 되었다. Tubocurarine의 AchBP 단백질 활성 부위에 대한 X,Y,Z Grid 값은 X=38.300689, Y=112.053467, Z=51.991022으로 나왔으나 actein과 actein 유도체들은 대부분 X=26.4, Y=127.3, Z=43.7 값 주변에 centroid grid를 형성하였다. 즉, tubocurarine이 결합하는 부위와는 다른 부위에 결합하여 AchBP의 활성에 영향을 주는 것으로 사료되었다. 이상의 연구 결과들을 분석해 볼 때, 아세틸콜린 수용체 길항제 tubocurarine보다 승마 추출물 생리 활성 물질인 actein과 그 유도체들이 보다 더 효율적인 아세틸콜린 수용체 길항제로 작용할 수 있음을 확인하였다. 결론적으로 승마 추출물 또는 actein 성분은 피부 주름 개선 효능을 지닌 보톡스를 대체하거나 또는 주름 개선용 화장품 신물질 연구 개발 분야에 효율적으로 활용할 수 있을 것으로 사료된다.

• Bulletin of the Korean Chemical Society
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• 제33권8호
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• pp.2741-2747
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• 2012

A new series of 2,5-disubstituted-1,3,4-thiadiazoles 6a-i was synthesized by overnight stirring various 1,4-disubstituted thiosemicarbazides 5a-i in polyphosphoric acid followed by neutralization. The structures of newly synthesized compounds 5a-i and 6a-i were characterized by IR, $^1H$ and $^{13}C$ NMR, elemental analysis and mass spectrometric studies. All the synthesized compounds were evaluated for their urease and acetylcholine esterase inhibition activities. Thiosemicarbazides 5a-i are found to possess excellent potential for urease inhibition, more than the standard drug. Thiosemicarbazides 5a-i are more potent urease inhibitor than their cyclic analogues thiadiazoles 6a-i. Almost all of the compounds are excellent inhibitors of acetylcholine esterase. The inhibition of acetylcholine esterase of compounds 5a, 5c, 5d, 5g, 5i, 6e, 6f, 6g, and 6i is much more than that of standard drug.

• 약학회지
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• 제44권1호
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• pp.80-86
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• 2000

TEA, glibenclamide, L-NAME and SKF 525A-induced contraction were investigated using acetylcholine, sodium nitroprusside (SNP, NO donor) and pinacidil (ATP sensitive $K^{+}$ channel opener) in rat abdominal and thoracic aorta. The relaxant effects of acetylcholine, SNP and pinacidil were not different in the abdominal aorta and in the thoracic aorta. Acetylcholine-induced relaxation was dependent on endothelial cell, but pinacidil was independent endothelia cell. In the presence of TEA, glibenclamide, L-NAME, mepacrine and SKF 525A, acetylcholine and SNP did not change, but pinacidil-induced relaxation was significantly reduced in presence of glibenclamide, which is ATP sensitive $K^{+}$ channel blocker. SKF 525A, which is inhibitor of cytochrome P$_{450}$ dependent epoxygenase, partially inhibited the pinacidil-induced relaxation. These results indicate that the pinacidil-induced relaxation may be mediated by ATP sensitive $K^{+}$ channel and partially by EETs, which is produced by cytochrome P$_{450}$ dependent epoxygenase.enase.