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방사선 조사 마우스에서 소장움세포의 Apoptosis 발생에 미치는 생약의 효과
김성호,안미라,나승렬,이종환,김재하,조성기,장종식,신동호 대한방사선 방어학회 2001 방사선방어학회지 Vol.26 No.1
Apoptosis의 유발을 억제하는 한약제를 파악하여 apoptosis와 관련된 정상적 또는 질병에 대한 연구에 자료를 제공하고자 방사선에 의해 유도된 apoptosis를 지표로 한의학적 처방에서 많이 사용되는 대표적 한약제(24종)의 효과를 검증하였다. 용안육, 산조인, 원지, 인삼, 복령, 목향, 천궁, 백작약, 승마, 시호 및 눈꽃동충하초 투여군에서 apoptosis는 감소되었으며, 이들 생약제는 apoptosis와 관련된 질병의 예방 및 치료에 적용할 수 있을 것이다. 추 후 이들 생약의 작용 기전에 대한 연구가 요구된다. This study was performed to determine the effect of several herbs on radiation-induced apoptosis in jejunal crypt cells. Longyanrou(Euphoris longana), Suanzaoren(Zizyphus vulgaris), Yuanzhi(Polygala tenuifolia), Rensan(Panax ginseng), Fuling(Poria cocos), Muxiang(Saussurea lappa), Chuanxiong(Cnidium officinale), Baishaoyao(Paeonia lactifolia), Shengma(Cimicifuga heracleifolia), Chaihu(Bupleurum falcatum) and Dongchongxiacao(Paecilomyces japonica) reduced the frequency of radiation-induced apoptosis(p<0.05). Although the mechanisms of this effect remain to be elucidated, these results indicated that Longyanrou, Suanzaoren, Yuanzhi, Rensan, Fuling, Muxiang, Chuanxiong, Baishaoyao, Shengma, Chaihu and Dongchongxiacao might be useful inhibitors of apoptosis, especially since these are relative nontoxic natural products.
[${\alpha}-Adrenergic$ and Cholinergic Receptor Agonists Modulate Voltage-Gated $Ca^{2+}$ Channels
Nah, Seung-Yeol,Kim, Jae-Ha,Kim, Cheon-Ho The Korean Society of Pharmacology 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.5
We investigated the effect of ${\alpha}-adrenergic$ and cholinergic receptor agonists on $Ca^{2+}$ current in adult rat trigeminal ganglion neurons using whole-cell patch clamp methods. The application of acetylcholine, carbachol, and oxotremorine ($50\;{\mu}M\;each$) produced a rapid and reversible reduction of the $Ca^{2+}$ current by $17{\pm}6%,\;19{\pm}3%,\;and\;18{\pm}4%$, respectively. Atropine, a muscarinic antagonist, blocked carbachol- induced $Ca^{2+}$ current inhibition to $3{\pm}1%$. Norepinephrine ($50\;{\mu}M$) reduced $Ca^{2+}$ current by $18{\pm}2%$, while clonidine ($50\;{\mu}M$), an ${\alpha}2-adrenergic$ receptor agonist, inhibited $Ca^{2+}$ current by only $4{\pm}1%$. Yohimbine, an ${\alpha}2-adrenergic$ receptor antagonist, did not block the inhibitory effect of norepinephrine on $Ca^{2+}$ current, whereas prazosin, an ${\alpha}1-adrenergic$ receptor antagonist, attenuated the inhibitory effect of norepinephrine on $Ca^{2+}$ current to $6{\pm}1%$. This pharmacology contrasts with ${\alpha}2-adrenergic$ receptor modulation of $Ca^{2+}$ channels in rat sympathetic neurons, which is sensitive to clonidine and blocked by yohimbine. Our data suggest that the modulation of voltage dependent $Ca^{2+}$ channel by norepinephrine is mediated via an α1-adrenergic receptor. Pretreatment with pertussis toxin (250 ng/ml) for 16 h greatly reduced norepinephrine- and carbachol-induced $Ca^{2+}$ current inhibition from $17{\pm}3%\;and\;18{\pm}3%\;to\;2{\pm}1%\;and\;2{\pm}1%$, respectively. These results demonstrate that norepinephrine, through an ${\alpha}1-adrenergic$ receptor, and carbachol, through a muscarinic receptor, inhibit $Ca^{2+}$ currents in adult rat trigeminal ganglion neurons via pertussis toxin sensitive GTP-binding proteins.
Ginsentology Ⅱ: Chemical Structure-Biological Activity Relationship of Ginsenoside
Seung-Yeol Nah,이병환 고려인삼학회 2007 Journal of Ginseng Research Vol.31 No.2
Since chemical structures of ginsenoside as active ingredient of Panaxdences have shown that ginsenoside is one of bio-active ligands through the diverse physiological and pharmacologicalevaluations. Chemical structure of ginsenoside could be divided into three parts depending on diol or triol ginsenoside:Steroid- or cholesterol-like backbone structure, carbohydrate portions, which are attached at the carbon-3, -6 or -20, andaliphatic side chain coupled to the backbone structure at the carbon-20. Ginsenosides also exist as stereoisomer at the car-about the relationship of chemical structure and biological activity. Recent reports have shown that ginsenoside Rg3, oneof active ginsenosides, exhibits differential physiological or pharmacological actions depending on its chemical struc-ture. This review will show how ginsenoside Rg3, as a model compound, is functionally coupled to voltage-gated ionchannel or ligand-gated ion channel regulations in related with its chemical structure.
α-Adrenergic and Cholinergic Receptor Agonists Modulate Voltage- Gated Ca<SUP>2 </SUP>Channels
Seung-Yeol Nah,Jae-Ha Kim,Cheon-Ho Kim 대한생리학회-대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.5
<P> We investigated the effect of α-adrenergic and cholinergic receptor agonists on Ca<SUP>2 </SUP>current in adult rat trigeminal ganglion neurons using whole-cell patch clamp methods. The application of acetylcholine, carbachol, and oxotremorine (50 ㄍM each) produced a rapid and reversible reduction of the Ca<SUP>2</SUP> current by 17⁑6%, 19⁑3%, and 18⁑4%, respectively. Atropine, a muscarinic antagonist, blocked carbachol- induced Ca<SUP>2</SUP> current inhibition to 3⁑1%. Norepinephrine (50 ㄍM) reduced Ca<SUP>2</SUP> current by 18⁑2%, while clonidine (50 ㄍM), an α<SUB>2</SUB>-adrenergic receptor agonist, inhibited Ca<SUP>2</SUP> current by only 4⁑1%. Yohimbine, an α<SUB>2</SUB>-adrenergic receptor antagonist, did not block the inhibitory effect of norepinephrine on Ca<SUP>2</SUP> current, whereas prazosin, an α<SUB>1</SUB>-adrenergic receptor antagonist, attenuated the inhibitory effect of norepinephrine on Ca<SUP>2 </SUP>current to 6⁑1%. This pharmacology contrasts with α<SUB>2</SUB>-adrenergic receptor modulation of Ca<SUP>2 </SUP>channels in rat sympathetic neurons, which is sensitive to clonidine and blocked by yohimbine. Our data suggest that the modulation of voltage dependent Ca<SUP>2 </SUP>channel by norepinephrine is mediated via an α<SUB>1</SUB>-adrenergic receptor. Pretreatment with pertussis toxin (250 ng/ml) for 16 h greatly reduced norepinephrine- and carbachol-induced Ca<SUP>2 </SUP>current inhibition from 17⁑3% and 18⁑3% to 2⁑1% and 2⁑1%, respectively. These results demonstrate that norepinephrine, through an α<SUB>1</SUB>-adrenergic receptor, and carbachol, through a muscarinic receptor, inhibit Ca<SUP>2 </SUP>currents in adult rat trigeminal ganglion neurons via pertussis toxin sensitive GTP-binding proteins.
Stereospecificity of Ginsenoside Rg3 Action on Ion Channels
Seung-Yeol Nah,Sang Min Jeong,Jun-Ho Lee,Jong-Hoon Kim,Byung-Hwan Lee,In-Soo Yoon,Joon-Hee Lee,김동현,임혜원,김양미 한국분자세포생물학회 2004 Molecules and cells Vol.18 No.3
Ginsenosides, active ingredients of Panax ginseng, exist as stereoisomers depending on the position of the hydroxyl group on carbon-20; i.e. 20(R)-ginsenoside and 20(S)-ginsenoside are epimers. We have shown previously that the mixture of 20(R)- and 20(S)-ginsenosides regulates ion channel activity. However, it was not clear which epimer was responsible. We investigated the structure- activity relationship of the ginsenoside Rg3 stereoisomers, 20-R-protopanaxatriol-3-[O-β-D-glucopyranosyl (1→2)-β-glucopyranoside], (20(R)-Rg3) and 20-S-protopanaxatriol- 3-[O-β-D-glucopyranosyl (1→2)-β-glucopyranoside], (20(S)-Rg3) in regulating voltage-dependent Ca2+, K+ or Na+ channel currents and 5-HT3A and α3β4 nicotinic acetylcholine (nACh) receptor channel currents expressed in Xenopus oocytes. 20(S)-Rg3 but not 20(R)-Rg3 inhibited the Ca2+, K+ and Na+ channel currents in a dose- and voltage-dependent manner. The fact that only 20(S)-Rg3 is active indicates that its hydroxyl group may be geometrically better aligned with the hydroxyl acceptor group in the ion channels than that of 20(R)-Rg3. However, both Rg3 stereoisomers inhibited 5- HT3A and α3β4 nACh receptor channel currents. These results indicate that the selectivity of action of the Rg3 stereoisomers differs between voltage-dependent and ligand-gated ion channels.
Seung-Yeol Nah,Byung-Hwan Lee,Sang-MIn Jung,Jun-Ho Lee,Jong-Hoon Kim,In-Soo Yoon,Joon-Hee Lee,Sun-Hye Choi,Sang-Mok Lee,Choon-Gon Chang,Hyung-Chun Kim,YeSun Han,백현동,김양미 한국분자세포생물학회 2005 Molecules and cells Vol.20 No.1
The flavonoid, quercetin, is a low molecular weight substance found in apple, tomato and other fruit. Besides its antioxidative effect, quercetin, like other flavonoids, has a wide range of neuropharmacological actions including analgesia, and motility, sleep, anticonvulsant, sedative and anxiolytic effects. In the present study, we investigated its effect on mouse 5-hydroxytryptamine type 3 (5-HT3A) receptor channel activity, which is involved in pain transmission, analgesia, vomiting, and mood disorders. The 5-HT3A receptor was expressed in Xenopus oocytes, and the current was measured with the two-electrode voltage clamp technique. In oocytes injected with 5-HT3A receptor cRNA, quercetin inhibited the 5-HT-induced inward peak current (I5-HT) with an IC50 of 64.7 ± 2.2 μM. Inhibition was competitive and voltage-independent. Point mutations of pretransmembrane domain 1 (pre-TM1) such as R222T and R222A, but not R222D, R222E and R222K, abolished inhibition, indicating that quercetin interacts with the pre-TM1 of the 5-HT3A receptor.