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      • Morphine과 Pentazocine의 혈장 Corticosterone 증가작용에 미치는 Naloxone 및 Diazepam의 영향

        전보권,박정율,조근행,김수경,Chun, Boe-Gwun,Park, Jung-Yul,Cho, Geun-Haeng,Kim, Soo-Kyung 대한약리학회 1983 대한약리학잡지 Vol.19 No.1

        The influences of diazepam and naloxone on the increase of plasma corticosterone level induced by morphine, pentazocine, ACTH, or picrotoxin were investigated in male mice. The results obtained were summarized as follows: 1) The increase induced by morphine or pentazocine of plasma corticosterone level was not affected by naloxone pretreatment but markedly suppressed by diazepam pretreatment. 2) The increase induced by ACTH of plasma corticosterone level was not affected by diazepam or naloxone pretreatment. 3) The picrotoxin markedly increased plasma corticosterone level, and the inceease was not affected by diazepam or naloxone pretreatment. This above results suggest that the increase induced by opioids of plasma corticosterone level seems to be rather related with other than opiate- or GABArerecptor.

      • Picrotoxin의 과혈당작용(過血糖作用)과 그에 대(對)한 몇 약물(藥物)의 영향(影響)

        전보권,Chun, Boe-Gwun 대한약리학회 1978 대한약리학잡지 Vol.14 No.1

        Ban formulated the concept of 'sympathetic center' and 'parasympathetic center' in the central nervous system, and Folkow et al. reported that the electric stimulation of the posterior part of hypothalamus induced the marked liberation of catecholamines from the adrenal medulla. Tatum reported that the hyperglycemic action of picrotoxin is contributed to the cathecholamines liberation from adrenal medulla by the excitation of hypothalamus via splanchnic nervous plexus. In this paper, the relationship between the convulsive action and the hyperglycemic effect of picrotoxin was investigated, with references to the influences of several drugs related with adrenergic function and two intravenous anesthetics on the picrotoxin hyperglycemia. The results obtained were summarized as follows; 1) There was no difference between the convulsive dose(1. 5mg/kg) and the subconvulsive dose (0.75mg/kg) of picrotoxin in its hyperglycemic effect that was not affected with the phenobarbital pretreatment, but the efficacy of its hyperglycemic action was more prominent than that of strychnine. 2) The hyperglycemic effect of picrotoxin was markedly suppressed by the pretreatment of thiopental or ketamine. 3) The hyperglycemic effect was not affected by the reserpine pretreatment, but the effect was markedly suppressed by the pretreatment of iproniazid or chlorpromazine. 4) The hyperglycemic effect of picrotoxin was significantly suppressed by the pretreatment of hexamethonium, propranolol or guanethidine, and the order of those suppressing efficacy was propranolol> hexamethonium> guanethidine.

      • KCI등재

        약물상호작용의 원리와 의의

        전보권,Chun, Boe-Gwun 대한생물정신의학회 2000 생물정신의학 Vol.7 No.1

        There is nothing that is harmless ; the dose alone decides that something is no poison(Paracelsus, 1493-1541). So, in a point of view to maximize the therapeutic efficacy of drug therapy in a way that minimize the drug toxicity, the knowledges of the drug-ineractions as well as the pharmacokinetic and pharmacodynamic principles of every therapeutic drug used in the medical clinic cannot be emphasized too much. Many drug interactions can be predicted if the pharmacokinetic properties, pharmacodynamic mechanisms of action of the interacting drugs are known, and most adverse interactions can be avoided. In this paper, the clinical importance, classification, and general principles of clinical drug-interactions are presentated with a few explanatory examples.

      • Influences of Hydrocortisone, DHEA, Estradiol and Testosterone on the Hepatic and Intestinal Polyamine Metabolism of Castrated Mice

        최상현,전보권,김남헌,천연숙,Choi, Sang-Hyun,Chun, Boe-Gwun,Kim, Nam-Hun,Chun, Yeon-Sook The Korean Society of Pharmacology 1990 대한약리학잡지 Vol.26 No.1

        웅성-마우스의 고환을 diethyl ether 마취하에서 제거하고, 수종의 steroid 홀몬을 각각 매일 1회씩 4일간 피하주사하여, 간 및 소장의 polyamine 함량과 소장의 diamine oxidase (DAO) 활성도에 미치는 그들의 영향을 검색하였다. 1. Hydrocortisone succinate 50 mg/kg (HC) 및 dehydroepiandrosterone 250 mg/kg (DHEA)에 의하여, 소장의 putrescine (PT)은 유의하게 증가되었으나, spermidine (SD) 및 spermine (SM)은 별 영향을 받지 않았고, 간의 SD은 다소 증가되고, SM은 다소 감소 되었으나, PT은 별 변동을 보이지 않았다. 2. Estradiol cypionate 5 mg/kg (E2)에 의하여, 간의 PT은 현저히 증가되었으나, 소장의 PT은 다소 증가되었고, 그외 소장 및 간의 SD와 SM의 변동은 보이지 않았다. Testosterone cypionate 5 mg/kg (TS)에 의하여는 간의 SD이 다소 감소되었을 뿐 별 변동이 없었다. 3. 소장의 DAO 활성도는 HC에 의하여 현저히 감소되었으나, E2 및 TS에 의하여는 유의하게 증가되었고, DHEA에 의하여는 별 영향을 받지않았다. 그러나 간의 monoamine oxidase 활성도는 HC, E2, DHEA, 및 TS에 의하여 영향을 받지 않았다. 4. Aminoguanidine 25 mg/kg로 소장의 DAO 활성도가 현저히 감소되었으나, 간 MAO 활성도는 영향을 받지 않았고, 소장의 PT 및 SD은 유의하게 증가되었으나, 간의 polyamine은 별 변동을 보이지 않았다. 이상의 결과로 미루어 볼때, 간 및 소장의 polyamine 대사-특히 PT 함량의 변동이 각각 E2 및 HC에 의하여 특이적으로 조절되는 바, E2에 의한 간 PT 함량의 증가는 주로 생성촉진 작용에 연유되며, HC에 의한 소장 PT 함량의 증가는 주로 polyamine의 이화성 대사를 억제함에 기인될 수 있는 것으로 사료된다. Hydrocortisone 50 mg/kg (HC), dehydroepiandrosterone 250 mg/kg (DHEA), ${\beta}-estradiol$ 5 mg/kg (E2), and testosterone 20 mg/kg (TS) were subcutaneously injected into the castrated ICR mice at noon for four days, and the animals were sacrificed at 10-12 A.M. of the fifth day. The intestinal DAO activity was significantly decreased by HC, but it was rather increased by E2 and TS, respectively. And DHEA did not change the DAO activity. But the hepatic MAO activity was not affected by anyone of HC, DHEA, E2, and TS. Aminoguanidine 25 mg/kg produced the marked decrease of the intestinal DAO activity and the significant increases of the intestinal PT and SD contents, but it did not change the hepatic polyamine contents. HC and DHEA induced the significant increase of the intestinal PT content. E2 induced the marked increase of the hepatic PT content and the moderate increase of the intestinal PT content. TS little affected the polyamine contents of the liver and intestine. These results suggest that the E2-induced increase of the hepatic PT content is rather ascribed to the greater enhancement of PT synthesis than the inhibition of polyamine catabolism, and that the HC-induced increase of the intestinal PT content is due partly to the inhibition of polyamine catabolism via DAO.

      • 신열판실험방법(新熱板實驗方法)에 의(依)한 Naloxone과 Diazepam이 Morphine 진통효과(鎭痛效果)에 미치는 영향(影響)에 관(關)한 검색(檢索)

        문영환,전보권,Moon, Young-Hwan,Chun, Boe-Gwun 대한약리학회 1982 대한약리학잡지 Vol.18 No.2

        Yeum et al. formulated a new hot-plate method using the threshold temperature, and there are some controversies on the effects of naloxone and diazepam on the antinociceptive action. In this paper, the comparison of three methods registering analgesic activity and the application of the new hot-plate method formulated by Yeum et al. on the study of the influences of naloxone and diazepam on the analgesic effect of morphine were tried in male mice. The results obtained were summarized as follows; 1) The least-square regression lines of the morphine analgesia plotted against log-dose showed the correlation coefficient of above 0.90, but the competitive antagonism produced by naloxone (0.1 mg/kg) against the analgesia was more prominently demonstated by the new hot-plate method than the other methods: original hot-plate method and electrical stimulation method. 2) In the experiment using the new hot-plate method, the log dose-response curve of morphine (y=7.30 x+49.80, r=0.998) was shifted to the right by the pretreatment of naloxone (0.1 mg/kg), but was slightly shifted to the left by the pretreatment of diazepam (2.5 mg/kg). This study suggests that for the analgesia experiment, the new hot-plate method is superior to the original hot-plate method or the electrical stimulation method, and that the potentiative effect of diazepam on the morphine anagesia is not significant.

      • Influences of Hydrocortisone, DHEA, Estradiol and Testosterone on the Polyamine Metabolism of Mouse Brain, Kidney, Liver and Intestine

        최상현,전보권,천종철,천연숙,Choi, Sang-Hyun,Chun, Boe-Gwun,Chun, Jong-Cheol,Chun, Yeon-Sook The Korean Society of Pharmacology 1991 대한약리학잡지 Vol.27 No.1

        웅성-마우스의 고환을 diethyl ether마취하에서 제거하고, 수종의 steroid 홀몬을 각각 매일 1회씩 4일간 피하주사한 다음 날의 오전 11-12 시에 뇌, 신장, 간장 및 소장의 polyamine을 검량하여 다음의 성적을 얻었다. 1. 고환절제-마우스(CM)에서, 소장 putrescine(PT)는 비고환절제-마우스(UCM)에 비하여 유의한 저하를 보였으나, 간 및 소장의 spermine(SM)은 오히려 유의하게 증가되었다. 2. Hydrocortisone 50 mg/kg는 UCM의 소장 PT는 현저히 증가시켰으나, CM의 뇌 PT 함량은 오히려 감소시켰다. 3. Estradiol 5 mg/kg는 UCM의 간 PT 함량을 현저히 증가시켰으며, CM에서는 간 PT 뿐만 아니라 신장의 전 polyamin 함량-증가와 아울러, 다소의 뇌 및 소장 PT-증가를 유도하였다. 4. Dehydroepiandrosterone 250 mg/kg(DHEA)와 testosterone 5 mg/kg(TS)는 UCM의 경우 신장 PT 함량만 유의하게 증가시켰으나, CM에서는 신장의 PT, spermidine(SD), 및 SM 모두를 더욱 현저히 증가시켰고, 아울러 DHEA는 간 SM의 감소를, TS는 뇌 SM의 유의한 증가를 유도하였다. 이상의 결과로 미루어 볼때, 간 및 소장의 polyamine대사-특히 PT함량의 변동은 각각 E2 및 HC에 의하여 보다 특이적으로 조절되고, 신장의 polyamine 대사는 성steroid들에 의하여 다소 비특이적인 조절을 받는 것으로 생각되며, 고환절제-마우스에서 나타나는 HC에 의한 뇌의 전potyamine감소 및 성steroid들에 의한 신장의 전polyamine증가의 발현기전에 대한 연구가 있어야 할 것으로 사료된다. The bilateral castration of male mice was operated under light ether anesthesia, and the sham operated mice were considered as the uncastrated. The treatments of mice with the following steroids were started one hour after operation. Hydrocortisone 50 mg/kg (HC), dehydroepiandrosterone 250 mg/kg (DHEA), ${\beta}-estradiol$ 5 mg/kg (E2), and testosterone 20mg/kg (TS) were subcutaneously injected into male ICR mice at noon for four days. Animals were sacrificed in the next-morning (at 10-12 A.M.) after the last injection. The intestinal putrescine(PT) content was lower and the liver and intestinal spermine(SM) contents were higher in castrated mice(CM), comparing with those of uncastrated mice (UCM). The intestinal PT content of UCM was markedly increased HC. But all brain polyamines of CM were significantly decreased by it. And HC also increased the spermidine(SD) content of kidney and liver and the intestinal PT content in CM. E2 induced the marked increase of liver PT content with the moderate increase of renal SD in UCM. And E2 significantly increased the brain and liver PT contents and the all renal polyamine contents in CM. Both of DHEA and TS induced the increase of renal PT content in UCM, and they also induced the marked increases of all renal polyamines of CM. In addition, TS increased the brain SM of CM. These results suggest that the steroidal regulation mechanism of brain, kidney, liver, and intestine seems to be different from one another, and the renal activity of polyamine synthesis can be markedly enhanced by sex steroids.

      • SCIESCOPUSKCI등재

        해마절편의 허혈성 $K^+$ 축적에 대한 $K^+$채널 조절 약물의 작용

        최진규,전보권,류판동,Choi, Jin-Kyu,Chun, Boe-Gwun,Ryu, Pan-Dong 대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.6

        Loss of synaptic transmission and accumulation of extracellular $K^+([K^+]_O)$ are the key features in ischemic brain damage. Here, we examined the effects of several $K^+$channel modulators on the early ischemic changes in population spike (PS) and $[K^+]_o$ in the CA1 pyramidal layer of the rat hippocampal slice using electrophysiological techniques. After onset of anoxic aglycemia (AA), orthodromic field potentials decreased and disappeared in $3.3{\pm}0.22\;min$ $(mean{\pm}SEM,\;n=40)$. The hypoxic injury potential (HIP), a transient recovery of PS appeared at $6.0{\pm}0.25\;min$ (n=40) in most slices during AA and lasted for $3.3{\pm}0.43\;min$. $[K^+]_o$ increased initially at a rate of 0.43 mM/min (Phase 1) and later at a much faster rate (12.45 mM/min, Phase 2). The beginning of Phase 2 was invariably coincided with the disappearance of HIP. Among $K^+$ channel modulators tested such as 4-aminopyridine (0.03, 0.3 mM), tetraethylammonium (0.1 mM), NS1619 $(0.3{\sim}10\;{\mu}M)$, niflumic acid (0.1 mM), glibenclamide $(40\;{\mu}M)$, tolbutamide $(300\;{\mu}M)$ and pinacidil $(100\;{\mu}M)$, only 4-aminopyridine (0.3 mM) induced slight increase of $[K^+]_o$ during Phase 1. However, none of the above agents modulated the pattern of Phase 2 in $[K^+]_o$ in response to AA. Taken together, the experimental data suggest that 4-aminopyridine-sensitive $K^+$channels, large conductance $Ca^{2+}-activated$ $K^+$ channels and ATP-sensitive $K^+$ channels may not be the major contributors to the sudden increase of $[K^+]_o$ during the early stage of brain ischemia, suggesting the presence of other routes of $K^+$ efflux during brain ischemia.

      • Inhibitory Effects of Amitriptyline, Sertraline and Chlorpromazine on the Thrombin-induced Aggregation of Platelets

        최상현,이영재,신경호,천연숙,전보권,Choi, Sang-Hyun,Lee, Young-Jae,Shin, Kyung-Ho,Chun, Yeon-Sook,Chun, Boe-Gwun The Korean Society of Pharmacology 1995 대한약리학잡지 Vol.31 No.3

        혈소판은 혈전기전의 중요요소로, monoamine성 신경전달물질의 대사에 있어서 신경계와 유사점을 가지고 있다. 따라서 항우울약물인 amitriptyline (AMT)과 sertraline (SRT)의 혈소판응집 억제와 이에 의한 세포내 신호전달 물질의 함량변동 및 단백인산화에 대한 영향을 chlorpromazine (CPZ)과 비교연구함으로써, 이들 약물의 혈소판응집 억제작용의 효능을 검정하고, 항 혈소판 및 항우울 작용기전의 일단을 규명하고자 하였다. SRT, CPZ 및 AMT은 thrombin (0.25 unit/ml)에 의한 혈소판응집을 억제하였으며, 각각의 IC50은 $4.37{\times}10^{-5}\;M$, $5.76{\times}10^{-5}\;M$ 및 $1.15{\times}10^{-4}\;M$이었다. 이러한 억제효과는 A23187$(1.0\;{\mu}M)$및 PMA(320 nM)에 의한 혈소판응집에 대해서도 유사하게 나타났다. thrombin은 혈소판응집과 아울러 thromboxane $B_2$ 및 $prostaglandin\;E_2$ 생성을 유의하게 증가시켰으며, 이러한 arachidonic acid 생성은 CPZ, AMT 및 SRT에 의하여 현저하게 억제되었다. CPZ, AMT 및 SRT은 cAMP 함량을 용량의존적으로 감소시켰으며, SRT, AMT $(1{\times}10^{-4}\;M)$ 및 CPZ $(3{\times}10^{-5}\;M)$은 cGMP 함량을 증가시키는 경향을 보였다. 한편, $Ins(1,4,5)P_3$ 함량은 thrombin 부하 후 10초 이내에 정점에 도달한 후 45초 이후까지 유지된다. CPZ과 AMT은 혈소판의 $Ins(1,4,5)P_3$ 함량을 현저히 증가시키며, thrombin에 의한 증가도 유의하게 증강시킨다. SRT은 혈소판의 $Ins(1,4,5)P_3$을 증가시키나, thrombin 부하 후 증강되지는 않았다. $Ins(1,4,5)P_3$ 증가에 이어서, $[Ca^{2+}]_i$은 thrombin 부하 후 20초에 최고점에 이르며, 이러한$[Ca^{2+}]_i$, 증가는 세 약물에 의하여 현저하게 억제되었다. 혈소판 단백인산화에 대해서, thrombin은 $41{\sim}43\;kDa$ 및 20kDa 단백인산화를 현저하게 증가시켰으며, 이는 AMT, SRT 및 CPZ에 의하여 억제되었다. CPZ, AMT 및 SRT 등의 세 약물은 유의한 항응집효과와 thromboxane생성억제 효과를 나타냈으며, 이들 약물에 의한 protein kinase C 활성억제 및 $Ins(1,4,5)P_3$의 함량증가는 각각 이들약물의 항응집효과 및 항우울성 작용기전과 연관될 수 있음을 시사한다. Platelets resemble monoaminergic neurons in several respects, i.e. the uptake of 5-HT and its inhibition, the subcellular storage and release of 5-HT, and the metabolism of aromatic amines brought about by monoamine oxidase. And the 5-HT content of rabbit platelets is well known to be about 40 times higher than that of human platelets. Therefore, this study was carried out to investigate the influences of amitriptyline (AMT) and sertraline (SRT) on the aggregation, contents of signaling second messengers, and protein phosphorylations of rabbit platelets in response to thrombin, 0.25 unit/ml, comparing with those of chlorpromazine (CPZ). Thrombin-induced aggregation was inhibited by SRT $(IC50:4.37{\times}10^{-5}\;M)$, CPZ $(IC50:5.76{\times}10^{-5}\;M)$, and AMT $(IC50:1.15{\times}10^{-4}\;M)$, respectively, and the aggregation by A23187 $(1.0\;{\mu}M)$ or PMA (320 nM) was also inhibited by SRT, CPZ, and AMT. AMT, SRT, and CPZ had little affects on basal contents of platelet $TXB_2$ and $PGE_2$, but all of them inhibited the thrombin-induced increase of $TXB_2$. Thrombin did not change the platelet contents of cAMP and cGMP. CPZ, AMT, and SRT produced the slight decrease of basal cAMP content, and their effects were not affected by thrombin-treatment. But SRT and AMT moderately increased the basal cGMP content, and the cGMP content of thrombin-stimulated platelets was gradually increased by the pretreatment with SRT, AMT, and CPZ. Particularly, the SRT-dependent increase of the cGMP content was notable. Platelet $Ins(1,4,5)P_3$ content was rapidly increased up to a plateau within 10 sec after thrombin-stimulation, AMT, SRT, and CPZ increased the basal $Ins(1,4,5)P_3$ content, and the thrombin-dependent increase was enhanced by pretreatment with CPZ and AMT, but was blunted by SRT. Platelet $[Ca^{2+}]_i$, was rapidly increased up to a peak level within 20 sec after thrombin-stimulation. The increase of $[Ca^{2+}]_i$ was sisnificantly inhibited by AMT, SRT, and CPZ. Thrombin- or PMA-induced phosphorylations of platelet $41{\sim}43\;kDa$ and 20 kDa proteins were significantly inhibited by AMT, SRT, and CPZ. These results suggest that the antiplatelet activities of AMT and CPZ may be considerably attributed to the inhibition of protein kinase C activity, and the activity of SRT may be associated with the inhibitory effect on the thrombin-induced increase of $Ins(1,4,5)P_3$ and the increasing effect on the cGMP content of ptatelets. Therefore, it seems to be evident that AMT and SRT may produce their antidepressant activity, at least, partly through the inhibition of protein kinase C activity or the increase of resting $Ins(1,4,5)P_3$, content and in case of SRT, to a lesser extent, via the increase of cGMP in the brain.

      • Hydrocortisone, DHEA, Estradiol 및 Testosterone에 의하여 나타나는 마우스-간 및 소장 Polyamine 대사의 변동에 관한 연구

        최상현(Sang-Hyun Choi),전보권(Boe-Gwun Chun),김남헌(Nam-Hun Kim),천연숙(Yeon-Sook Chun) 대한약리학회 1990 대한약리학잡지 Vol.26 No.1

        웅성-마우스의 고환을 diethyl ether 마취하에서 제거하고, 수종의 steroid 홀몬을 각각 매일 1회씩 4일간 피하주사하여, 간 및 소장의 polyamine 함량과 소장의 diamine oxidase (DAO) 활성도에 미치는 그들의 영향을 검색하였다. 1. Hydrocortisone succinate 50 mg/kg (HC) 및 dehydroepiandrosterone 250 mg/kg (DHEA)에 의하여, 소장의 putrescine (PT)은 유의하게 증가되었으나, spermidine (SD) 및 spermine (SM)은 별 영향을 받지 않았고, 간의 SD은 다소 증가되고, SM은 다소 감소 되었으나, PT은 별 변동을 보이지 않았다. 2. Estradiol cypionate 5 mg/kg (E2)에 의하여, 간의 PT은 현저히 증가되었으나, 소장의 PT은 다소 증가되었고, 그외 소장 및 간의 SD와 SM의 변동은 보이지 않았다. Testosterone cypionate 5 mg/kg (TS)에 의하여는 간의 SD이 다소 감소되었을 뿐 별 변동이 없었다. 3. 소장의 DAO 활성도는 HC에 의하여 현저히 감소되었으나, E2 및 TS에 의하여는 유의하게 증가되었고, DHEA에 의하여는 별 영향을 받지않았다. 그러나 간의 monoamine oxidase 활성도는 HC, E2, DHEA, 및 TS에 의하여 영향을 받지 않았다. 4. Aminoguanidine 25 mg/kg로 소장의 DAO 활성도가 현저히 감소되었으나, 간 MAO 활성도는 영향을 받지 않았고, 소장의 PT 및 SD은 유의하게 증가되었으나, 간의 polyamine은 별 변동을 보이지 않았다. 이상의 결과로 미루어 볼때, 간 및 소장의 polyamine 대사-특히 PT 함량의 변동이 각각 E2 및 HC에 의하여 특이적으로 조절되는 바, E2에 의한 간 PT 함량의 증가는 주로 생성촉진 작용에 연유되며, HC에 의한 소장 PT 함량의 증가는 주로 polyamine의 이화성 대사를 억제함에 기인될 수 있는 것으로 사료된다. Hydrocortisone 50 mg/kg (HC), dehydroepiandrosterone 250 mg/kg (DHEA), β-estradiol 5 mg/kg (E2), and testosterone 20 mg/kg (TS) were subcutaneously injected into the castrated ICR mice at noon for four days, and the animals were sacrificed at 10-12 A.M. of the fifth day. The intestinal DAO activity was significantly decreased by HC, but it was rather increased by E2 and TS, respectively. And DHEA did not change the DAO activity. But the hepatic MAO activity was not affected by anyone of HC, DHEA, E2, and TS. Aminoguanidine 25 mg/kg produced the marked decrease of the intestinal DAO activity and the significant increases of the intestinal PT and SD contents, but it did not change the hepatic polyamine contents. HC and DHEA induced the significant increase of the intestinal PT content. E2 induced the marked increase of the hepatic PT content and the moderate increase of the intestinal PT content. TS little affected the polyamine contents of the liver and intestine. These results suggest that the E2-induced increase of the hepatic PT content is rather ascribed to the greater enhancement of PT synthesis than the inhibition of polyamine catabolism, and that the HC-induced increase of the intestinal PT content is due partly to the inhibition of polyamine catabolism via DAO.

      • Effects of Single and Repeated Electroconvulsive Shock on the Acetylcholine and Polyamine Contents in Temporal Cortex and Decorticated Cerebrum of Mice

        최상현,이학회,박청산,전보권,천연숙,Choi, Sang-Hyun,Lee, Hak-Hee,Park, Chung-San,Chun, Boe-Gwun,Chun, Yeon-Sook The Korean Society of Pharmacology 1991 대한약리학잡지 Vol.27 No.1

        뇌에 대한 경련성 전기충격(electroconvulsive shock: ECS)을 이용한 치료가 시작된 후, 50여년에 걸처 이의 생물학적 작용에 대한 연구가 있었으나, 이렇다할 결과가 아직 없으며, 특히 뇌의 신경전달물질중 가장 중요한 것으로 인정되는 acetylcholine의 함량이 ECS로 증가되는지 감소되는지 확실치 않다. 더욱이, 대체로 조직의 재생능에 비례하는 함량의 증감을 보이는 polyamine함량이 가장 재생능이 미약한 뇌에 고농도로 있으며 뇌의 국소에 따라서도 그 함량에 큰 차가 있고, 뇌의 polyamine-합성 또한 ECS에 의하여 촉진된다고 하는데, 최근에 Zawia와 Bondy는 polyamine-대사가 뇌-신경의 장기적 적응현상에 관련됨을 제시하였다. 따라서 본 연구에서는 웅성 ICR계 생쥐에 ECS(13mA, 100cps, 1sec)를 단회(1 ECS)-부하하여 나타나는 변동을 검색하고 그 결과를 5회(매일 1회씩 이틀마다 5회: 5 ECS)-부하하여 얻은 것과 비교-검토하였다. 측뇌-피질(temporal cortex: $TC{\acute{x}}$)과 피질을 제거한 대뇌(decorticated cerebrum: dc-CB)의 acetylcholine(ACh)함량이 1 ECS 부하후 각각 10분 및 30분에 79.9 및 49.4% 증가되었으며, 이 증가가 5 ECS 부하시에는 유의하게 감약되었던 바, 특히 TCx에서 더욱 현저하였다. Polyamine의 경우, putrescine함량은 TCx 및 dc-CB에서 1 ECS 및 5 ECS 어느 부하에 의하여도 별 변동을 보이지 않았으나 spermidine(Sd) 및 spermine(Sm)은 1 ECS 후에 다소 감소되었을 뿐 아니라 그 감소의 크기가 5 ECS 후에는 현저히 증폭되었고, 특히 dc-CB에서 더욱 현저하였다. 또한 ECS를 4회-부하하고 24시간 후의 Sd및 Sm 함량은 ACh 함량과 달리 정상치에 비하여 유의하게 낮았으며, 따라서 ECS에 의한 ACh함량-변동에 미치는 Sm(30mg/kg, 복강내주사)의 영향을 관찰하였던 바 별 변화를 볼 수 없었다. 이상의 성적은 반복되는 ECS에 대하여 대뇌의 ACh 및 polyamine대사가 각각 특이적인 적응성 변동을 보임을 시사하는 것으로 사료된다. There are some rather conflicting reports correlating ECS-induced changes of brain acetylcholine, and recently, Zawia and Bondy(1990) proposed the biological role of polyamine system in the long-term adaptive responses of brain to electrical stimulation. This study was undertaken to evaluate the effects of a single or repeated ECS(10mA, 100cps, 1sec; 5 ECS spread out over 9 days) on the brain acetylcholine(ACh) and polyamine contents of male mice. The ACh contents of temporal cortex(TCx) and decorticated cerebrum(dc-CB) were markedly increased by 79.9% and 49.4%, respectively, 10 and 30 min after ECS, and the increases were significantly attenuated with repeated 5 ECS, particularly in dc-CB. The putrescine concentrations of both TCx and dc-CB were little different and not affected by 1 ECS or 5 ECS. But the spermidine(Sd) concentration was higher in dc-CB and spermine(Sm) higher in TCx. While they were moderately decreased after 1 ECS, and their decreases were accentuated after 5 ECS, particularly in dc-CB.Sm(30mg/kg, i.p. inject. 30min before ECS) did not affect the ECS-induced increase of ACh content. Thease results suggest that both of brain ACh and polyamine may be implicated with the long-term adaptive responses to electrical stimulation

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