• 한국동물위생학회지
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• 제14권1호
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• pp.71-77
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• 1991

Parathion is widely used in agriculture, but it is highly toxic and now clear that parathion behaves like a cholinergic drug by inhibiting the enzyme cholinesterase. In order to know acute toxicity and the changes of cholinesterase activity according to time lapsed in Sprague-Dawley rats injected single with half dose to LD$_{50}$ of parathion, cholinesterase activities in serum, spinal cord, whole brain and median lethal dose between sex difference were investigated. The results obtained were summerized as follows ; 1. 4LD_{50}$ values of parathion given intraperitoneally to male and female rats were 10.5mg / kg(95% confidence limits, 6.6-16.8mg/ kg) and 3.3mg/ kg(95% confidence limits, 1.9-5.6mg/ kg). 2. The inhibition rate of cholinesterase activities in serum of parathion-injected rats according to time lapsed were peakly decreased to 35.4%(male) and 32.4%(female) after 1 hour in comparison to control group, but cholinesterase activities were completely recovered after 48 hours. 3. The inhibition rate of cholinesterase activities in spinal cord of parathion-injected rats according to time lapsed were peakly decreased to 31.1% (male) and 36.3% (female) after 30 minutes in comparison to control group, but cholinesterase activities were completely recovered after 48 hours. 4. The inhibition rate of cholinesterase activities in whole brain of parathion -injected rats according to time lapsed were peakly decreased to 32.2%(male) and 42.6%(female) after 1 hour in comparison to control group, but cholinesterase activities were completely recovered after 48 hours.s.

• 대한약리학회지
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• 제28권1호
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• pp.11-18
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• 1992

Physostigmine을 급성(0.75 mg/kg), 7일간 매일 1회(0.75 mg/kg) 그리고 7일간 연속(0.15 mg/kg/h) 투여한 쥐의 선조체에 있어서 dopamine(DA) 및 대사체와 tyrosine hydroxylase(TH)활성도의 변화를 검색하였다. 급성 투여 1시간 후 선조체의 DA 농도는 변화가 없었으나 dihydroxy-phenylacetic acid(DOPAC)과 homovanillic acid(HVA)농도는 증가하였다. 또한 DA의 turnover의 증가를 제시하는 DOPAC/DA와 HVA/DA의 비율도 증가하였다. 그러나 TH활성도는 24시간 후 감소를 나타내었다. Physostigmine을 매일 및 연속 투여군에서는 DA과 대사체의 농도에는 변화가 없었으나, DA의 turnover의 감소를 제시하는 DA과 대사체의 비율은 감소하였다. 그러나 TH활성도는 매일 투여군에서만 감소를 나타내었다. 이러한 결과는 physostigmine을 급성 및 아급성으로 투여시 dopamine대사의 변화가 있음을 제시한다. 또한 콜린 신경계의 아급성 자극은 dopamine 대사 및 활성도를 감소 시킬 가능성을 시사해 주었다.

• The Korean Journal of Physiology and Pharmacology
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• 제18권1호
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• pp.47-53
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• 2014

In this study, we propose that diprophylline exerts bidirectional modulation (BM) on the isolated rat jejunal segment depending on its contractile state. The results supported the hypothesis. Diprophylline ($20{\mu}M$) exerted stimulatory effects on the contractility of jejunal segment in six low contractile states while inhibitory effects in six high contractile states, showing the characteristics of BM. Diprophylline-induced stimulatory effect was significantly blocked by atropine, indicating the correlation with cholinergic activation. Diprophylline-induced inhibitory effect was partially blocked by phentolamine, propranolol, and L-N-Nitro-Arginine respectively, indicating their correlation with sympathetic activation and nitric oxide-mediated relaxing mechanisms. Diprophylline-induced BM was abolished by tetrodotoxin or in a $Ca^{2+}$ free condition or pretreated with tyrosine kinase inhibitor imatinib, suggesting that diprophylline-induced BM is $Ca^{2+}$ dependent, and that it requires the presence of enteric nervous system as well as pacemaker activity of interstitial cells of Cajal. Diprophylline significantly increased the reduced MLCK expression and myosin extent in constipation-prominent rats and significantly decreased the increased MLCK expression and myosin extent in diarrhea-prominent rats, suggesting that the change of MLCK expression may also be involved in diprophylline-induced BM on rat jejunal contractility. In summary, diprophylline-exerted BM depends on the contractile states of the jejunal segments, requires the presence of $Ca^{2+}$, enteric nervous system, pacemaker activity of interstitial cells of Cajal, and MLCK-correlated myosin phosphorylation. The results suggest the potential implication of diprophylline in relieving alternative hypo/hyper intestinal motility.

• 한국동물위생학회지
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• 제15권1호
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• pp.58-66
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• 1992

The insecticide p-nitropheny diethyl thiophospate is alse known by the symbol E.605 and a legion of trade names including “parathion”. The insecticide is widely used in agriculture, but it is highly toxic and now clear that parathion behaves like a cholinergic drug by inhibiting the enzyme cholinesterase. In order to know acute toxicity and the changes of glucose concentrations and activity according to time lapsed in female mice given orally single with the half dose to $LD_{50}$ of parathion, glucose contents and cholinesterase activities in serum as well as cholinesterase activities in whole brain and spinal cord were investigated, otherwise median lethal dose ($LD_{50}$) of parathion given orally against female mice was determined. The results obtained were summerized as follows ; 1. $LD_{50}$ value of parathion given orally to female mice was 7.1mg/kg(95% confidence limits, 3.8-13.1mg/kg) 2. The inhibition rate of cholinesterase activities in serum of parathion-administrated mice according to time lapsed were peakly decreased to 61% after 30 minutes in comparison to control group, but activities were completely recovered after 48 hours. 3. The inhibition rate of cholinesterase activities in whole brain of parathion-administrated mice according to time lapsed were peakly decreased to 49% after 2 hours in completely recovered after 24 hours. 4. The inhibition rate of cholinesterase activities in spinal cord of parathion-administrated mice according to time lapsed were peakly decreased to 57% after 2 hours in comparison to control group, but activities were completely recovered after 48 hours. 5. The changes of glucose contents in serum of parathion-administrated mice according to time lapsed and in directly after death due to parathion poisoning were no significantly difference.

• Journal of Microbiology and Biotechnology
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• 제31권1호
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• pp.51-62
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• 2021

Here, we investigated the prebiotic and antioxidant effects of Actinidia arguta sprout water extract (AASWE) on lipopolysaccharide (LPS)-induced cognitive deficit mice. AASWE increased viable cell count, titratable acidity, and acetic acid production in Lactobacillus reuteri strain and showed a cytoprotective effect on LPS-induced inflammation in HT-29 cells. We assessed the behavior of LPS-induced cognitive deficit mice using Y-maze, passive avoidance and Morris water maze tests and found that administration of AASWE significantly improved learning and memory function. The AASWE group showed antioxidant activity through downregulation of malondialdehyde levels and upregulation of superoxide dismutase levels in brain tissue. In addition, the AASWE group exhibited activation of the cholinergic system with decreased acetylcholinesterase activity in brain tissue. Furthermore, AASWE effectively downregulated inflammatory mediators such as phosphorylated-JNK, phosphorylated-NF-κB, TNF-α and interleukin-6. The major bioactive compounds of AASWE were identified as quercetin-3-O-arabinopyranosyl(1→2)-rhamnopyranosyl(1→6)-glucopyranose, quercetin-3-O-apiosyl(1 → 2)-galactoside, rutin, and 3-caffeoylquinic acid. Based on these results, we suggest that AASWE not only increases the growth of beneficial bacteria in the intestines, but also shows an ameliorating effect on LPS-induced cognitive impairment.

• 한국식품과학회지
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• 제47권6호
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• pp.779-784
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• 2015

본 연구는 천연 식물이 기억력 개선에 미치는 영향을 검토하기 위하여 총 7가지 식물에 대하여 아세틸콜린분해효소 활성 억제력을 측정하였다. 특히 미나리 알코올추출물(18.76%)의 억제력이 가장 우수하였으며, 미나리 알코올추출물에 대한 추가 연구를 수행하였다. Tg2576 마우스의 기억력에 미치는 영향을 검토하기 위하여 미나리 알코올추출물 50 mg/kg으로 3개월간 경구투여 후 수동회피테스트로 인지기능변화를 측정하였고, 뇌 속의 아세틸콜린분해효소 활성 억제, 베타아밀로이드1-42 단백질 생성 억제력을 측정하였다. 그 결과, 수동회피 테스트에서 미나리추출물을 투여한 Tg 마우스군은 181.77초로 생리식염수를 투여한 Tg 마우스군과 비교하여 머무름 시간이 유의적으로 증가하게 나타났다. 베타아밀로이드1-42 단백질 농도 측정 시 미나리 알코올추출물에 의하여 축적 농도가 985.19 pmol/g으로 감소하였으며, 생리식염수를 투여한 Tg 마우스군과 유의적 차이가 있었다. 추가적인 효소 억제력 실험 결과, 미나리 알코올추출물의 아세틸콜린분해효소 활성억제에 대한 50% 활성억제농도($IC_{50}$)값은 $991.77{\mu}g/mL$로 나타났으며, Lineweaver-Burk Plot 결과, 무경쟁적 저해로 나타났다. 따라서 미나리 알코올추출물은 Tg2576 형질전환 마우스의 인지기능을 개선시키며, 콜린성 신경시스템을 보호하는 물질로 판단된다. 미나리 알코올추출물은 기억 및 학습 증진에 효과적으로 작용하는 천연식물로써 이상의 결과를 근거로 한 미나리 소재의 다양한 기능성제품 개발과 부가가치 향상이 가능할 것으로 판단된다.

• Journal of Chest Surgery
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• 제20권1호
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• pp.112-127
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• 1987

Myasthenia gravis is a neuromuscular transmission function disorder characterized by fatigue and weakness of voluntary muscles. This muscular weakness is intensified by activity and stress, and improved by the use of anticholinesterase compounds. It was initially described by Erb in 1879 and later named myasthenia gravis by Jolly in 1895. Although the pathogenesis is Known to be an autoimmune related reduction in the number of available acetylcholine receptors at neuromuscular junctions, the role of thymus in myasthenia gravis is still unclear and under investigation. Thymectomy in the management of myasthenia gravis has become increasingly important since Dr. Blalock observed in 1939 that some patients with thymic tumors and myasthenia gravis improved following thymectomy. A clinical study of 102 cases of myasthenia gravis was performed at Yonsei University College of Medicine. Seoul, Korea from Jan. 1976 to Jun. 1986. In order to determine which factors are of prognostic significance, attention is focused upon pre-operative patient evaluation, problems in operative and post-operative care, and long-term follow-up observations. The results were as follows: 1. The sex distribution was 67 females and 35 males, the mean age of onset was 28.95*1.69 years, and the maximal incidence occurred between 21 and 40 years of age [56 cases: 54.9%]. 2. Clinical manifestations of ocular symptoms were seen to 70 patients [68.6%] extremities weakness in 33 [32.3%], bulbar weakness in 29 [28.4%], and dyspnea in 13 [12.7%]. 3. Study cases more than two thirds were classified as mild types [MG 1 and MG 11A] and 6 cases as grave [MG 1V] based on the modified Osserman`s classification system, 4. Thymectomy was performed in 19 cases which presented in severe myasthenia symptoms and showed no improvement with cholinergic drugs. Histologic examination of the excised thymus glands revealed no abnormalities in 4 cases, thymic hyperplasia in 5, benign thymoma in 5, and malignant thymoma in 5. 5. Immediate post-operative complications included 2 cases of pneumothorax which were treated by tube thoracostomies, there was no operative mortality. 6. The response to cholinergic drugs in 36 cases younger than 20 years old and in 27 cases older than 40 years was relatively poor, while that in 35 cases between the ages of 21 and 40 years old was good. 7. Thirty of 39 cases in groups IIB, III & IV improved markedly with medical or surgical management while only 16 of 59 cases in the mild groups [I and IIA] improved, almost all surgical cases improved in all categories. 8. There were 5 deaths. occurring between 7 months and 3 years 3 months of treatment of myasthenia gravis. The causes of death were myasthenic crisis in 2 cases, respiratory failure due to candidiasis & radiation pneumonitis in one case, cerebral hemorrhage due to high blood pressure in two case.

• Archives of Pharmacal Research
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• 제23권4호
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• pp.353-359
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• 2000

${\alpha}_2$-Adrenoceptor antagonists, which can enhance synaptic norepinephrine levels by blocking feedback inhibition processes, are potentially useful in the treatment of disease states such. as depression, memory impairment, impotence and sexual dysfunction. (10bS)-1,2,3,5,6,10b-Hexahydropyrrolo[2,1-a]isoquinoline oxalate (YSL-3S) was evaluated in several in vitro biological tests to establish its pharmacological profile of activities as an ${\alpha}_2$-adrenoceptor antagonist. Saturation binding assay revealed that$^{3}[H]$rauwolscine bound to the $\alpha$$_2$-adrenoceptors with a Kd value of 6.3$\pm$0.5 nM and a Bmax value of 25l$\pm$39 fmol/mg protein in rat cortical synaptic membranes. Competitive binding assay showed that YSL-3S inhibited the binding of$^3[H]$rauwolscine (1 nM) in a concentration-dependent manner with a Ki value of 98.2$\pm$12.1 nM while it did not inhibit the binding of [$^3$H]cytisine (1.25 nM) to neuronal nicotinic cholinergic receptors. The Ki values of yohimbine, clonidine and norepinephrine for $^3[H]$rauwolscine binding were 15.8$\pm$1.0, 40.1$\pm$5.9 and 40.0$\pm$11.5 nM, respectively. In addition, the binding affinity of YSL-3S for ${\alpha}_2$-adrenoceptors was higher than that of its antipode and the racemic mixture. The functional activity of YSL-3S at the presynaptic ${\alpha}_2$-adrenoceptors was assessed using the prostatic portion of the rat vas deferens. Clonidine inhibited field-stimulated contractions of the vas deference in a dose-dependent manner. The presence of YSL-3S or yohimbine caused a parallel, rightward the dose-response curve of clonidine in a dose-dependent manner, indicating an antagonistic action at the presynaptic ${\alpha}_2$-adrenoceptors. The $pA_2$values of yohimbine and YSL-3S were 7.66$\pm$0.13 and 6.64$\pm$0.18, respectively. The results indicate that YSL-3S acts as a competitive antagonist at presynaptic ${\alpha}_2$ -adrenoceptors with a potency approximately ten times lower than yohimbine, but is devoid of binding affinity for neuronal nicotinic cholinergic receptors.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1988년도 학술대회지
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• pp.55-62
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• 1988

본 연구에서 한국산 인삼의 활성성분의 하나인 panaxadiol(PD)의 가토적출분신에서 카테콜아민(CA)의 분비작용과 작용기전을 파악하고자 실험을 시행하여 다음과 같은 결과를 얻었다. PD($400\;{\mu}g$)을 가토적출부신에 투여 하였을 때 카테콜아민의 분비를 유의성 있게 증가시켰다. PD의 이러한 CA분비작용은 atiropine처리로 현저히 억제되었다. Physostigmine 처리시 PD뿐만 아니라 Ach의 CA 분비작용은 뚜렷이 증가 되었다. 그러나 chlorisondamine처리로 PD나 Ach의 분비효과는 억제되었다. 또한 PD($400\;{\mu}g$/30min)을 주입한 후에 Ach의 CA분비작용은 증강되었다. Ouabain에 의해서 PD의 작용은 약화되었으나 Ach의 CA분비효과는 오히려 강화되었다. PD나 Ach의 작용은 adenosine 전처리시 현저히 증강되었다. EDTA(5mM)와 함께 Ca-free Krebs액으로 30분 주입한 경우에 Ach의 분비작용은 거의 전적으로 차단되었으며, PD의 작용도 약화되었다. 이상의 실험결과로 보아, PD는 가토적출부신에서 $Ca^{++}$의존적으로 CA분비를 증가시키며, PD의 이러한 작용은 부신내의 cholinergic muscarinic 및 nicotinic receptor의 흥분작용에 기인되고, chromaffin cell에 대한 일부 직접작용에 의해서 나타나는 것으로 사료된다.

• The Korean Journal of Physiology
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• 제15권2호
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• pp.91-96
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• 1981

The wormwood is one of the plants which occur widely throughout the world. Though the precise data on the entire chemical composition of mugwort leaves are not available, the major principles which have been found so far include inulin, alkaloid, thujon, sesquiterpene and several vitamins. Santonin, a parasiticide, is one of the glucosides extracted from the limited species of wormwood. It has long been known in herb medicine that the plants of this family has not only strong hemostatic, analgesic and parasiticidal actions but also therapeutic effects for diarrhea, stomachache and asthma. In recent pharmaceutical botany the wormwood is introduced to have antipyretic and astringent actions also. The mugwort(Artemisia asiatica Nakai) is the most common species of wormwood that occurs in Korea. The usage of this edible leaves of mugwort is rather various. It is used not only for wormwood bath but also as forage, moxa and medicinal agents. Recently Kim et al reported from their study on the effect of mugwort on the motility of isolated intestine of rabbits that tonus and motility were markedly enhanced by mugwort but this effect of mugwort on intestinal motility was almost completely blocked by atropine suggesting that activity of mugwort was exerted through its cholinergic effect. It was the findings of Kim et al that prompted the authors to do the present experiment. The present study was undertaken to investigate effects of mugwort(Artemisia asiatica Nakai) juice on the respiration and blood pressure in cats. And also studied was the mechanism of depressor action of Artemisia asiatica Nakai Juice (AAJ). The results obtained are as follows; 1) It was observed that mean arterial blood pressure and heart rate were decreased markedly by AAJ. Following administration of 0.15 ml/kg and 0.3 ml/kg AAJ into cats the maximum depressor responses observed were $77.5{\pm}2.2\;mmHg$ and $94.0{\pm}3.7\;mmHg$ respectively. 2) Depressor responses to AAJ were blocked markedly by atropine whereas the responses were not affected by propranolol and dibenamine. Therefore it is strongly inferred that depressor action of AAJ results mainly from its cholinergic effect. This inference was further substantiated by the fact that heart rate change which invariably accompanies depressor responses to AAJ was almost completely abolished by atropinization. 3) After administration of AAJ into cats frequency of respiration was markedly increased while depth of respiration decreased during first 2-3 seconds.