Glucose Modulation of Release of Endogenous Catecholamines from Hypothalamic Fragments in Vitro

정전섭,황형식,위명복,송동근,김용식,김영희,Jung, Jun-Sub,Hwang, Hyung-Sik,Wie, Myung-Bok,Song, Dong-Keun,Kim, Yong-Sik,Kim, Yung-Hi The Korean Society of Pharmacology 1993 대한약리학잡지 Vol.29 No.2

시상하부 조각에서 카테콜아민의 분비에 대한 포도당의 영향을 관찰하였다. 카테콜아민의 기초분비는 포도당의 농도$(5{\sim}30mM)$에 반비례하였다. Tetrodotoxin $(10\;{\mu}M)$의 존재하에서 카테콜아민의 기초분비에 대한 포도당의 억제 작용은 대부분 유지되었으나, 도파민에 대한 30 mM 포도당의 억제 작용은 거의 봉쇄되었다. Tetrodotoxin $(10\;{\mu}M)$과 desipramine $(3\;{\mu}M)$의 존재하에서는 카테콜아민의 기초분비에 대한 포도당의 영향이 없었다. 이상의 결과는 포도당이 transsynaptic action 뿐 아니라 카테콜아민 신경세포 말단에 대한 직접 작용을 통하여 카테콜아민의 분비를 조절할 것임을 시사한다. 카테콜아민의 분비에 대한 포도당의 조절작용은 당뇨상태에서의 시상하부 카테콜아민 대사의 변화를 적어도 부분적으로는 설명할 수 있으리라 사료된다. Effects of glucose on the catecholamine release from the hypothalamic fragments in vitro were studied. Basal release of catecholamines was inversely related to the concentrations $(5{\sim}30\;mM)$ of glucose in the incubation medium. Glucose did not affect the 30 mM $K{^+}-stimulated$ release of catecholamine. In the presence of tetrodotoxin $(10\;{\mu}M)$, the inhibitory effect of glucose on the basal release of catecholamines was largely persisted, but the inhibitory effect of 30 mM glucose on dopamine release was largerly blocked. In the presence of both tetrodotoxin $(10\;{\mu}M)$ and desipramine $(3\;{\mu}M)$, glucose failed to affect the basal catecholamine release. The results suggest that glucose modulates the catecholamine release through a direct action on the catecholaminergic nerve terminals, as well as through a trans-synaptical action. The glucose-modulation of the catecholamine release may explain, at least in part, the diabetes-induced changes in the hypothalamic catecholamine metabolism.

공황장애 및 주정의존 환자들의 혈장 Serotonin과 5-HIAA 농도에 대한 연구

문석환,송동근,유태혁,박상욱,김영희,최인근,정전섭 大韓神經精神醫學會 1995 신경정신의학 Vol.34 No.1

To investigate the serotonergic function of alcohol dependence patients with that of panic disorder patients, the plasma serotonin and 5-HIAA were measured by HPLC method. The subjects were panic disorder patients (N-8), alcohol dependence patients (N=10) and normal controls(N=10). The results were as follow : 1) Alcohol dependence patients showed lower plasma serotonin concentrations than the other two groups. 2) Alcohol dependence patients had the highest plasma 5-HIAA concentrations among the three groups. and panic disorder patients had higher plasma 5-HAA concentrations than controls. 3) The ratio of serotonin/5-HIAA in the plasma were lowest in alcohol dependence patients among the three groups, and were lower in panic disorder patients than in normal controls. 4) The total amounts of plasma serotonin and 5-HIAA showed no differences among the three group. From the results, there were significant differences among alcohol dependence patients, panic disorder patients and normal controls in the ratios of serotonin/5HIAA in the plasma. Alcohol dependence patients had higher rate of serotonin metabolism than the normal controls and alcohol dependence and panic disorder patients had biological similarity in serotonin metabolism suggesting abnormal serotonergic system, different from that of normal controls.

시상하부 조각에서 내재성 카테콜아민의 분비에 대한 포도당의 조절작용

정전섭(Jun-Sub Jung),황형식(Hyung-Sik Hwang),위명복(Myung-Bok Wie),송동근(Dong-Keun Song),김용식(Yong-Sik Kim),김영희(Yung-Hi Kim) 대한약리학회 1993 대한약리학잡지 Vol.29 No.2

시상하부 조각에서 카테콜아민의 분비에 대한 포도당의 영향을 관찰하였다. 카테콜아민의 기초분비는 포도당의 농도(5 ~ 30mM)에 반비례하였다. Tetrodotoxin (10μM)의 존재하에서 카테콜아민의 기초분비에 대한 포도당의 억제 작용은 대부분 유지되었으나, 도파민에 대한 30 mM 포도당의 억제 작용은 거의 봉쇄되었다. Tetrodotoxin (10μM)과 desipramine (3μM)의 존재하에서는 카테콜아민의 기초분비에 대한 포도당의 영향이 없었다. 이상의 결과는 포도당이 transsynaptic action 뿐 아니라 카테콜아민 신경세포 말단에 대한 직접 작용을 통하여 카테콜아민의 분비를 조절할 것임을 시사한다. 카테콜아민의 분비에 대한 포도당의 조절작용은 당뇨상태에서의 시상하부 카테콜아민 대사의 변화를 적어도 부분적으로는 설명할 수 있으리라 사료된다. Effects of glucose on the catecholamine release from the hypothalamic fragments in vitro were studied. Basal release of catecholamines was inversely related to the concentrations (5 ~ 30 mM) of glucose in the incubation medium. Glucose did not affect the 30 mM K⁺-stimulated release of catecholamine. In the presence of tetrodotoxin (10μM), the inhibitory effect of glucose on the basal release of catecholamines was largely persisted, but the inhibitory effect of 30 mM glucose on dopamine release was largerly blocked. In the presence of both tetrodotoxin (10μM) and desipramine (3μM), glucose failed to affect the basal catecholamine release. The results suggest that glucose modulates the catecholamine release through a direct action on the catecholaminergic nerve terminals, as well as through a trans-synaptical action. The glucose-modulation of the catecholamine release may explain, at least in part, the diabetes-induced changes in the hypothalamic catecholamine metabolism.

생쥐에서 5-Hydroxytryptophan에 의한 설사에 대한 각종 전통 생약 추출물의 억제 효과

유재선,정전섭,이태희,손건호,서홍원,송동근,김영희,Yoo, Jae-Sun,Jung, Jun-Sub,Lee, Tae-Hee,Son, Kun-Ho,Suh, Hong-Won,Song, Dong-Keun,Kim, Yung-Hi 한국생약학회 1995 생약학회지 Vol.26 No.4

To find serotonin(5-hydroxytryptamine, 5-HT)-antagonizing activities in traditional herbal drugs, crude extracts from 66 kinds of traditional herbal drugs were randomly screened for inhibitory effects on 5-hydroxytryptophan(HTP)-induced diarrhea in mice. Intraperitoneal injection of 5-HTP(2.5 mg/kg) induced diarrhea in 92% of mice, when observed from 10 to 15 min after injection. Crude extracts(2 g/kg) from 66 kinds of traditional herbal drugs were orally pretreated for 1 h before 5-HTP injection. Of the 66 herbal drugs screened, Ephedrae Herba(麻黃), Cimicifugae Rhizoma(升麻), Anisi stellati Fructus(八角茴香), Aurantii Fructus(枳實), Polygalae Radix(遠志) showed the most potent inhibiting activities against 5-HTP(2.5 mg/kg)-induced diarrhea in mice. There are at least 3 possible mechanisms that would be responsible for the inhibitory effect of crude extracts on 5-HTP-induced diarrhea; 1) crude extract-induced inhibition of the activity of aromatic aminoacid decarboxylase catalyzing the conversion of 5-HTP to 5-HT, 2) crude extract-induced blockade of 5-HT receptor(s) in the gastrointestinal tract responsible for 5-HTP-induced diarrhea, 3) crude extract-induced inhibition of gastrointestinal activity, irrespective of 5-HT system. The exact mechanisms and molecules, responsible for the inhibitory effect of crude extracts on 5-HTP-induced diarrhea remain to be clarified.

Lipidomic analysis of plasma lipids composition changes in septic mice

안원균,정전섭,송동근 대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.4

A lipidomic study on extensive plasma lipids in bacterial peritonitis (cecal ligation and puncture, CLP)-induced sepsis in mice was done at 24 h post-CLP. The effects of administration of lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), compounds known to have beneficial effects in CLP, on the sepsis-induced plasma lipid changes were also examined. Among the 147 plasma lipid species from 13 lipid subgroups (fatty acid [FA], LPA, LPC, lysophosphatidylethanolamine [LPE], phosphatidic acid [PA], phosphatidylcholine [PC], phosphatidylethanolamine [PE], phosphatidylinositol [PI], monoacylglyceride [MG], diacylglyceride [DG], triacylglyceride [TG], sphingomyelin [SM], and ceramide [Cer]) analyzed in this study, 40 and 70 species were increased, and decreased, respectively, in the CLP mice. Treatments with LPC and LPA affected 14 species from 7 subgroups, and 25 species from 9 subgroups, respectively. These results could contribute to finding the much needed reliable biomarkers of sepsis.

배양된 흰쥐 뇌간 신경세포에서 5-Hydroxytryptamine 흡수에 대한 각종 전통 생약 추출물의 억제 효과

조현미,정전섭,이태희,손건호,서홍원,송동근,김영희,Cho, Hyun-Mi,Jung, Jun-Sup,Lee, Tae-Hee,Son, Kun-Ho,Suh, Hong-Won,Song, Dong-Keun,Kim, Yung-Hi 한국생약학회 1995 생약학회지 Vol.26 No.4

Crude methanolic(80%) extracts from 109 kinds of traditional herbal drugs were randomly screened for inhibitory effects on 5-hydroxytryptamine(5-HT) uptake in primary cultured rat brainstem neurons. Rat brainstem neurons were cultured from embryonic day 14, and maintained for 7-9 days in vitro. Clomipramine (500 nM), a reference drug, decreased 5-HT uptake to 16% of control values. Of the 109 herbal drugs screened, Citri immaturi Pericarpium(靑皮), Coptidis Rhizoma(黃蓮), Cnidii Rhizoma(土川芎) showed the most potent 5-HT uptake inhibiting activities. These herbal drugs, at the concentration of $10{\;}{\mu}g/ml$, inhibited 5-HT uptake 69, 69, and 57% respectively, when inhibition(%) was expressed as a relative value compared to the 500 nM clomipramine-induced inhibition.

Effects of Long - Term Administration of Panax ginseng - Ethanol Extracts in Mice

이강미,위명복,정전섭,송동근,김영희 생화학분자생물학회 1992 생화학분자생물학회 춘계학술발표논문집 Vol.- No.-

The mixture of Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge. extract produces analgesic and anti-inflammatory effects in a collagen-induced arthritis mouse model

Jing-Hui Feng,정전섭,황승환,이수경,이상윤,곽연길,김두호,송추연,김민정,서홍원,김성찬,임순성 한국통합생물학회 2022 Animal cells and systems Vol.26 No.4

Pain and inflammation typically manifest in patients with arthritis. It is now widely known that Agrimonia pilosa Ledeb (AP) and Salvia miltiorrhiza Bunge (SM) exert anti-inflammatory and antinociceptive effects. We have previously reported that the mixture extract (ME) from AP and SM produces antinociceptive and anti-inflammatory effects in gout arthritis and monoiodoacetate (MIA)-induced arthritis models. In the present study, we assessed the antinociceptive and anti-inflammatory effects on the collagen-induced arthritis (CIA) model. The antinociceptive effects in mice were measured using the von Frey test. ME administered once or for one week (once per day) once, and one-week reduced the pain in a dose-dependent manner (from 50 to 100 mg/kg) in the CIA-induced osteoarthritis (OA) model. ME treatment also reduced tumor necrosis factor (TNF)-α and C-reactive protein (CRP) levels in plasma and ankle tissues. Furthermore, COX-1, COX-2, NF-κB, TNF-α, and IL-6 expressions were attenuated after ME treatment. In most experiments, the antinociceptive and anti-inflammatory effects induced by ME treatment were almost equal to or slightly better than those induced by Perna canaliculus (PC) treatment, which was used as a positive control. Our results suggest that ME possesses antinociceptive and anti-inflammatory effects, indicating its potential as a therapeutic agent for arthritis treatment.

Decreased in vivo Tyrosine Hydroxylase Activities with Normal Norepinephrine Levels in Streptozotocin-Induced Diabetic Rat Hypothalamus

위명복,송동근,강병태,정전섭,최연식,박준형,김영희,Wie, Myung-Bok,Song, Dong-Keun,Kang, Byung-Tae,Jung, Jun-Sub,Choi, Yeun-Sik,Park, Joon-Hyoung,Kim, Yung-Hi The Korean Society of Pharmacology 1991 대한약리학잡지 Vol.27 No.1

We studied changes in the hypothalamic norepinephrine(NE) metabolism in streptozotocin (STZ)-induced diabetic rats by measuring basal NE levels, turnover rate of NE, and in vivo tyrosine hydroxylase activities. Basal NE level did not change significantly upto 4 weeks after the establishment of diabetes with STZ(60 mg/kg, iv). But turnover rate of NE decreased to 62% of control rate(P<0.01), and in vivo tyrosine hydroxylase activities decreased to 32% of control level(P<0.05) at one week of diabetes. From these results, we concluded that, of the three parameters measured, in vive tyrosine hydroxylase activity is the most sensitive index of altered hypothalamic NE metabloism in STZ-induced diabetic rats. Streptozotocin(STZ)-유발 당뇨쥐에서 시상하부의 norepinephrine(NE) 대사를 기초 NE 함량, NE 교체율, in vivo tyrosine hydroxylase(TH) 활성을 그 지표로 하여 조사하였다. STZ (60 mg/kg, iv)로 당뇨를 유발한 후 4주까지 기초 NE 함량은 유의한 변화가 없었다. 그러나 당뇨유발 후 1주째에 측정한 NE 교체율은 대조치의 62%(p<0.01), in vivo TH 활성은 대조치의 34% (p<0.05)로 감소하였다. 이상의 결과로 본 실험에서 측정한 NE 대사의 세 지표 중에서 in vivo TH 활성이 STZ-유발 당뇨쥐의 시상하부 NE 대사의 변화를 가장 민감하게 반영하였다.

Study of the Antinociception Induced by Opioids and the Proenkephalin Gene Expression in Spontaneously Hypertensive Rats

서홍원,이태희,송동근,최성란,정전섭,김영희,Suh Hong-Won,Lee Tae-Hee,Song Dong-Keun,Choi Seong-Ran,Jung Jun-Sub,Kim Yung-Hi The Korean Society of Pharmacology 1995 대한약리학잡지 Vol.31 No.1

8주, 18주, 그리고 32주된 Spontaneously Hypertensive Rats (SHR)과 Wistar-Kyoto Rats(WKY)과의 blood pressure(혈압)를 측정하여본 결과 SHR 그룹이 WKY에 비해 19에서 70 mmHg 차이로 SHR 그룹이 WKY group에 비하여 혈압이 높았다. 18주된 SHR과 WKY에서 제 3 뇌실내 (intraventricular)로 투여된 morphine과 ${\beta}-endorphin$의 진통작용을 검색하여 보았다. WKY group에 비하여 SHR group에서 뇌실내로 투여된 ${\beta}-endorphin$은 진통작용에 있어서 상승작용 (potentiation)을 보임을 발견하였고 뇌실내로 투여된 morphine은 SHR group에서 약간만 상승작용을 보였다. SHR과 WKY group간에 opioid의 진통작용에 있어서 중요한 역할을 하는 Midbrain과 Medulla (pons), 그리고 spinal cord (척수)의 lumbar부위의 $[Met^5]-enkephalin$과 proenkep-halin A mRNA level을 측정하여 보았다. SHR과 WKY group간의 $[Met^5]-enkephalin$과 proenkephalin mRNA의 양은 별로 차이를 보이지 않았다. 이러한 결과로 미루어 볼때 SHR group에서 뇌실내로 투여된 ${\beta}-endorphin$은 그의 진통효과에 있어서 보인 상승작용은 척수상부에 위치하고 있는 opioid deptide의 양이 변해서가 아니라 다른 기전에 의하여 조절되어지고 있음을 시사한다. The present studies were carried out to determine if antinociceptive action of morphine and ${\beta}-endorphin$ administered intraventricularly was changed in. pentobarbital anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Antinociception was assessed by the tail-flick test. The $ED_{50}$ values of antinociception for morphine administered intraventricularly were 1.9 and 1.2 nmol for WKY and SHR rats, respectively. The $ED_{50}$ values of antinociception for ${\beta}-endorphin$ administered intraventricularly were 0.40 and 0.12 nmol for WKY and SHR rats, respectively. The $[Met^5]-enkephalin$ (ME) and proenkephalin mRNA levels in midbrain, pons and medulla, or lumbar section of the spinal cord in WKY and SHR rats were measured by the radioimmunoassay and Northern blot assay, respectively. There were no differences of ME and proenkephalin mRNA levels in these tissues between WKY and SHR rats. The results suggest that ${\beta}-endorphin$ but not morphine administered intraventricularly produces a greater antinociception in SHR rats. This increased antinociceptive effect of ${\beta}-endorphin$ in SHR rats may be not, at least, due to the alterations of ME And proenkephalin mRNA levels in the midbrain, pons and medulla, or spinal cord.