가토심근(家兎心筋) Mitochondria 분획내(分劃內) Adenosine triphosphatase 활성도(活性度)에 대(對)한 Diphenylhydantoin sodium 및 Quinidine의 작용(作用)

홍기환,Hong, Ki-Whan 대한약리학회 1972 대한약리학잡지 Vol.8 No.1

The author studied the actions of ouabain and diphenylhydantoin sodium on the ATPase activity in mitochondrial fraction isolated from rabbit heart and compared with that of quinidine. The results obtained are as follows: 1) In studying the $(Na^++K^+)-activated$ ATPase activity, the rabbit heart isolated was immediately frozen for 7-9 days (ageing of preparation) and thereafter the mitochondria1 fraction obtained by differential centrifugation technic was treated with solution A containing 0.15% deoxycholate for 24-48 hours at $-10^{\circ}C$ before using in experiment. These methods increased the activity ratio to 0.87-0.98. 2) The $(Na^++K^+)-activated$ ATPase activity in mitochondrial fraction of rabbit heart was not completely but markedly inhibited by ouabain. This inhibitory action of ouabain was moderately antagonised by $K^+$ concentration at constant Na concentration. 3) Diphenylhydantoin sodium in concentration of $5{\times}10^{-4}{\sim}10^{-3}M$ stimulated markedly not only $Mg^{++}-dependent$ ATPase activity but also $(Na^++K^+)$-activated ATPase activity and in concentration lower than $10^{-6}M$ had little effect. However, this effect of diphenylhydantoin was markedly increased in the presence of $Na^+$ alone rather than $K^+$ alone, but lesser than that effect in the presence of both $Na^+$ and $K^+$, together. The stimulating effect of diphenylhydantoin was specifically antagonized by ouabaion. 4) When the rabbits were intravenously injected with ouabain and diphenylhydantion respectively, $(Na^++K^+)-activated$ ATPase activity of rabbit heart of ouabain-treated group was much decreased and both $(Na^++K^+)-activated$ ATPase and $Mg^{++}-activated$ ATPase activity were moderately increased in diphenylhydantoin-treated rabbit group. 5) The $(Na^++K^+)-activated$ ATPase activity in mitochondrial fraction of rabbit heart was slightly inhibited by quinidine in high concentration of $10^{-4}M$, but nearly little effect was observed below the concentration of $5{\times}10^{-5}M$. 6) It might be possible to conclude that diphenylhydantoin specifically antagonised the action of ouabain on the membrane ATPase, which is different from the action of quinidine.

Role of Endothelium-derived Relaxing Factor in Cerebral Autoregulation in vivo

홍기환,유성숙,임병용,Hong Ki-Whan,Yu Sung-Suk,Rhim Byung-Yong The Korean Society of Pharmacology 1995 대한약리학잡지 Vol.31 No.1

In anesthetized rats, we examined the possibility that endothelium-derived relaxing factor (EDRF) or nitric oxide (NO) released in response to cholinergic mechanism may contribute to the reflex autoregulation of cerebral blood flow. Suffusion with mock cerebrospinal fluid (CSF), containing acetylcholine (ACh, $10^{-9}{\sim}10^{-6}M$) evoked concentration-dependent vasodilatation of the resting pial artery (mean, $19.3{\pm}1.7{\mu}m$, n=36), which was significantly inhibited not only by $N{\omega}$-nitro-L-arginine (L-NNA, $10^{-5}M$) but also by methylene blue ($10^{-6}M$) and oxyhemoglobin ($10^{-6}M$). The muscarinic receptors in the endothelium of pial artery implicated in the release of EDRF were considered to be $M_1\;and\;M_3$ subtypes. When suffused with mock CSF containing L-arginine it caused a transient vasodilatation, which was strongly inhibited by LY 83583 ($10^{-5}M$), but not by L-NNA ($10^{-5}M$). Additionally, both ACh- and L-arginine-induced vasodilation were significantly inhibited by glibenclamide, a specific ATP-sensitive $K^+$ channel blocker. On the other hand, changes in pial arterial diameter were plotted as a function of changes in systemic arterial blood pressure. The slopes of regression lines for vasodilation and vasoconstriction were not affected by pretreatment with $10^{-5}M$ L-NNA, but significantly reduced by $3{\times}10^{-6}M$ glibenclamide. Thus it is suggested that the reflex vasodilation of rat pial arteries in response to a transient hypotension is not mediated by EDRF (NO). 본 연구에서는 콜린성 기전에 반응하여 분비되는 내피 의존성 이완물질(endothelium-derived relaxing factor, EDRF)나 nitric oxide(NO)가 마취 흰쥐의 뇌혈류 자가조절기전에 관여할 가능성을 관찰하였다. Acetylcholine($10^{-9}-10^{-6}M$)을 포함한 mock 뇌척수액(CSF)을 관류시 뇌연막 동맥은 농도에 의존하여 이완반응 나타내었고(평균; $19.3{\pm}1.7{\mu}m$, n=36), 이러한 이완반응은 $N{\omega}$-nitro-L-arginine(L-NNA, $10^{-5}M$)에 의해서 억제되었을 뿐 아니라 methylene blue($10^{-6}M$)나 oxyhemoglobin($10^{-6}M$)에 의하여도 억제되었다. 한편 이러한 acethlcholine에 의한 뇌연막동맥의 이완반응을 매게하는 무스카린 수용체는 무스카린 수용체 길항제의 봉쇄효과를 관찰한 실험에서 $M_1$과 $M_3$ 아형으로 생각되었다. L-Arginine을 함유한 mock CSF로 관류시 일어나는 일시적인 혈관이완반응은 NY 83583 ($10^{-5}M$)에 강력히 억제되었으나 L-NNA ($10^{-5}M$)에 의해서는 억제되지 아니하였다. 한편 acetylcholine과 L-arginine에 의한 혈관이완반응은 ATP-sensitive $K^+$ 통로 봉쇄제인 glibenclamide에 의해 유의하게 봉쇄되었다. 나아가 뇌연막동맥의 직경 변화를 동맥압의 변화에 대하여 검정한 결과 혈관이완과 혈관수축의 희귀 직선의 경사도는 $10^{-5}M$ L-NNA의 전처치에 의하여 영향을 받지 아니하였으나, $3{\times}10^{-6}M$ glibenclamide에 의해 유의하게 감소되었다. 이러한 결과로 보아 혈압하강에 대해 쥐의 뇌연막동맥에 나타나는 혈관이완반응은 EDRF(NO)에 의해 매개되지 않는다고 사료된다.

Chronic Cadmium Administration Preferentially Affects the Responsiveness Mediated by Pre- and Post-synatic ${\alpha}_2$-Adrenoceptors

홍기환,임병용,손의동,Hong, Ki-Whan,Rhim, Byung-Yong,Sohn, Uy-Dong The Korean Society of Pharmacology 1985 대한약리학잡지 Vol.21 No.1

전기자극에 의한 적출 정관의 수축 또는 뇌척수제거 흰쥐의 심박동수 증가가 카드뮴 장기투여 (매격일 $10{\mu}$ mols, 1회씩 2주간 복강내 주사)로 인하여 대조군에 비하여 현저히 항진되었다. 이러한 전기자극에 의한 반응은 ${\alpha}_2$-효현제인 clonidine에 의하여 억제 되었고, 이 억제는 ${\alpha}_2$-길항제인 yohimbine 투여로 봉쇄되었다. 나아가 methoxamine에 의한 확장 혈압의 증가는 카드뮴 투여에 의하여 영향을 받지 아니하였으나 clonidine에 의한 증가는 카드뮴 투여에 의하여 억제되었다. 이러한 결과로 보아 카드뮴 장기 노출에 의하여 시납스 전 및 후 ${\alpha}2-adrenoceptors$가 우선적으로 억제되었다고 시사되는 바이다. Either the contraction of isolated was deferens or the increase of heart rate in the pithed rats induced by electrical stimulation was significantly augmented by cadmium administration (10 ${\mu}mols$ of cadmium acetate every other day for 2 weeks i.p.). These stimulation-induced responses were diminished by ${\alpha}_2$-adrenoceptor agonist, clonidine, and the inhibition was antagonized by yohimbine. Furthermore, the increase in diastolic blood pressure by clonidine was also significantly reduced after cadmium administration, whereas that by methoxamine was not influenced with this dose range of cadmium. With these results it may be postulated that the long-term cadmium exposure may preferentially affect the responsiveness of the presynaptic as well as the postsynaptic ${\alpha}_2$-adrenoceptors.

가토(家兎) 및 백서자궁(白鼠子宮)의 Adrenotropic Receptors에 관(關)한 연구(硏究)

홍기환,Hong, Ki-Whan 대한약리학회 1966 대한약리학잡지 Vol.2 No.1

The author studied the adrenotropic receptors of the non-pregnant uteri of the rabbit and rat, using epinephrine (alpha and beta activator), phenoxybenzamine(alpha blocking agent) and nethalide (beta blockade), and obtained the following results: 1. The spontaneous motility of isolated non-pregnant uteri from rabbits were stimulated by epinephrine, whereas that of isolated non-pregnant rat uterus was inhibited by epinephrine. 2. Both alpha and beta adrenergic receptors were present in the uterine muscle of both animals. 3. In the non-pregnant rabbit uterus, alpha receptors were predominant, whereas in the non -pregnant rat uterus, beta receptors preponderated over alpha receptors.

Prostaglandins와 여성생식기(女性生殖器) 계통(系統)

홍기환,김해성,Hong, Ki-Whan,Kim, Hae-Sung 대한약리학회 1975 대한약리학잡지 Vol.11 No.1

The recent knowledge about the effects and the biological roles of prostaglandins(PGs) in the female reproductive system were reviewed on the following view points in detail and the authors also argued on the efficacy and reliability for the induction of labour and therapeutic abortions in midtrimester pregnancy. 1. The actions of PGs on the myometrium in vivo and in vitro and the effects of ovarian hormones on the actions of PGs. 2. The actions of PGs on the fallopian tube. 3. The role of PGs in the initiation of menstrual bleeding and dysmenorrhea. 4. The biological action of PGs on the mechanism of labour and parturition. 5. The efficacy and reliability of PGs for therapeutic abortion in the first and midtrimester pregnancy. 6. The biological role of PGs in the activity and life-span of corpus luteum.

적출(摘出) 기니아-픽 정관(精管)에 있어서 교감신경효능제(交感神經效能劑)의 作用(작용)에 대(對)한 Prostaglindin E₁의 강화작용(强化作用)

홍기환(Hong, Ki-Whan),강영수(Kang, Young-Soo) 대한약리학회 1974 대한약리학잡지 Vol.10 No.1

기니아-픽 및 백서정관(白鼠精管)에 대(對)한 PGE₁의 작용(作用)과 이들 조직(組織)에 있어서 교감신경효능제(交感神經效能劑)의 작용(作用)에 미치는 PGE₁의 효과(效果)를 보고 나아가서 계양막(鷄羊膜)에 대(對)한 PGE₁의 작용(作用)을 관찰(觀察)하였다. 1. 기니아-픽 적출정관표본(摘出精管標本)에서 PGE₁전처치(前處置)에 의(依)하여 phenylephrine이나 norepinephrine의 작용(作用)이 증강(增强)되었으며, 하복신경(下腹神經)-근표본(筋標本)에서 신경자극(神經刺戟)이나 trans-mural stimulation에 의(依)한 수축(收縮)에 미치는 phenylephrine, norepinephrine 및 tyratnine의 작용(作用)이 PGE₁ 전처치(前處置)에 의(依)하여 증강(增强)되었다. 특히 긴장상승(緊張上昇)이 현저(顯著)하였다. 2. 백서정관(白鼠精管)의 하복신경(下腹神經)-근표본(筋標本)에서는 기너아-픽 정관(精管)에서와는 달리 PGE₁을 처리(處理)함으로써 신경자극(神經刺戟) 및 transmural stimulation에 의(依)한 수축고(收縮高)가 서서(徐徐)히 감소(減少)되고, PGE₁을 전처치(前處置)한 후(後)에도 10^-6g/ml phenylephrine 또는 norepinephrine에 의(依)한 긴장상승(緊張上昇)이나 수축고(收縮高)의 증가(增加)는 나타나지 아니 하였다. 3. 신경섬유(神經纖維)가 제거(除去)된 기니아-픽정관(精管)에 있어서는 PGE₁ 전처치(前處置)에 의(依)하여 phenylephrine 또는 norepinep. hrine의 작용(作用)이 증가(增加)되나 denervation 된 백서(白鼠)의 정관(精管)에 있어서는 PGE₁ 처리(處理)로서는 norepinephrine의 작용(作用)에 하등(何等)의 영향(影響)을 주지 아니 하였다. 4. 계양막평활근(鷄羊膜平滑筋)의 자발운동(自發運動)은 저농도(低濃度) PGE₁(10^-8g/ml)에 의(依)하여 거의 변화(變化)를 받지 아니 하나, 농도(濃度)가 增加(增加)함으로서 자발운동(自發運動)은 불규칙(不規則)하나 대체(大體)로 억제적(抑制的)으로 나타났었고, PGE₁ 전처치후(前處置後) 고농도(高濃度) phenylephrine을 작용(作用)시켰으나 하등(何等)의 영향(影響)을 받지 아니 하였고 physostigmine의 작용(作用)은 길항(拮抗하였다. 이상(以上)의 결과(結果)로 보아 PGE₁은 동물(動物)의 정관(精管)에 대(對)한 작용(作用)에는 종(種)의 차이(差異)가 있으며 PGE₁은 교감신경효능제(交感神經效能劑)에 의(依)한 기니아-픽 정관수축작용(精管收縮作用)에 대(對)하여 supersensitivity를 야기(惹起)시켰으며, 이는 정관평활근(精管平滑筋)에 대(對)한 직접작용(直接作用)이 아닌 다른 작용기전(作用機轉)에 기인(基因)할 것으로 사료(思料)되는 바이다. 1. The authors investigated the effects of PGE₁ on the action of sympathomimetics in the vas deferens of guinea-pig, comparing with those in the rat vas deferens, and also the action of PGE₁ on the motility of nerve-free smooth muscle of chick amnion. 2. In the isolated guinea-pig vas deferens, the actions of phenylephrine and norepinephrine were much potentiated by pretreatment with PGE₁. Futher, in the isolated hypogastric nerve-vas deferens preparation of guinea-pig, effects of phenylephrine, norepinephrine and tyramine on the contractile response of vas to the hypogastric nerve stimulation and to the transmural stimulation were also augumented especially in tension by PGE₁-pretreatment. 3. In the isolated hypogastric nerve-vas preparation of rat, both contractile responses to hypogastric nerve and transmural stimulation were slowly reduced by treatment with PGE₁ and the potentiated effect of phenylephrine or norepinephrine was not observed in spite of pretreatment with PGE₁. 4. The actions of phenylephrine and norepinephrine on the denervated vas deferens of guinea-pig were also enhanced by PGE₁ as it were in the intact vas deferens, but there was no significant effect by PGE₁ on the action of norepinephrine in the denervated rat vas deferens. 5. PGE₁ in low concentration (10^-8g/ml) did not affect the spontaneous motility of nerve-free smooth muscle of chick amnion (9~11 th day incubated chick), but in large concentration (5 X 10^-8g/ml) it caused irregular and slightly inhibitory movement. Pretreatment with PGE₁ on chick amnion did not exert any change on the action of phenylephrine applied. However, the stimulatory action of physostigmine on the chick amnion was a little antagonized by the low concentration of PGE₁. 6. It might be summarized that there is species difference between the actions of PGE₁ on the vas deferens of guinea-pig and that of rat, and the action of PGE₁ on the guinea-pig vas deferens might be mediated by the other mechanism rather than by direct action on the vas musculature.

백서자궁(白鼠子宮)의 Adrenotropic Receptor에 관(關)한 추보(追補)

홍기환(Hong, Ki-Whan),김규태(Kim, Kyu-Tae),이종사(Lee, Chong-Sa) 대한약리학회 1967 대한약리학잡지 Vol.3 No.1

Supplemental studies were made on the adrenotropic receptors of the rat uterus, using adrenergic activators such as phenylephrine, norepinephrine, epinephrine, and isoproterenol and adrenergic blocking agents such as phenoxybenzamine and inderal. The studies have revealed the following results : 1. Phenylephrine, norepinephrine, epinephrine, and isoproterenol inhibited the spontaneous motility of the isolated rat uterus in the following order : Isoproterenol>epinephrine>norepinephrine>phenylephrine. 2. The inhibitory responses of the isolated rat uterus to phenylephrine and epinephrine were abolished by the pretreatment with phenoxybenzamine. 3. The inhibitory responses of the isolated rat uterus to isoproterenol and epinephrine were not affected by phenoxybenzamine. 4. The motility of the isolated rat uterus pretreated with inderal was stimulated by phenylephrine, norepinephrine and epinephrine. 5. The inhibitory responses of the isolated rat uterus to isoproterenol were abolished by the pretreatment with inderal. 6. The motility of the isolated rat uterus pretreated with inderal and phenoxybenzamine was not affected by phenylephrine, norepinephrine and epinephrine. 7. It is, therefore, concluded that the rat uterus has both alpha excitatory and beta inhibitory receptors, with beta inhibitory receptors predominating.

뇌혈류 자가조절에 대한 Endothelium-derived Relaxing Factor의 역할

홍기환(Ki Whan Hong),유성숙(Sung Suk Yu),임병용(Byung Yong Rhim) 대한약리학회 1995 대한약리학잡지 Vol.31 No.1

본 연구에서는 콜린성 기전에 반응하여 분비되는 내피 의존성 이완물질(endothelium-derived relaxing factor, EDRF)나 nitric oxide(NO)가 마취 흰쥐의 뇌혈류 자가조절기전에 관여할 가능성을 관찰하였다. Acetylcholine(10^-9-10^-6M)을 포함한 mock 뇌척수액(CSF)을 관류시 뇌연막 동맥은 농도에 의존하여 이완반응 나타내었고(평균; 19.3 ± 1.7μm, n=36), 이러한 이완반응은 N{\omega}-nitro-L-arginine(L-NNA, 10^-5M)에 의해서 억제되었을 뿐 아니라 methylene blue(10^-6M)나 oxyhemoglobin(10^-6M)에 의하여도 억제되었다. 한편 이러한 acethlcholine에 의한 뇌연막동맥의 이완반응을 매게하는 무스카린 수용체는 무스카린 수용체 길항제의 봉쇄효과를 관찰한 실험에서 M₁과 M₃ 아형으로 생각되었다. L-Arginine을 함유한 mock CSF로 관류시 일어나는 일시적인 혈관이완반응은 NY 83583 (10^-5M)에 강력히 억제되었으나 L-NNA (10^-5M)에 의해서는 억제되지 아니하였다. 한편 acetylcholine과 L-arginine에 의한 혈관이완반응은 ATP-sensitive K⁺ 통로 봉쇄제인 glibenclamide에 의해 유의하게 봉쇄되었다. 나아가 뇌연막동맥의 직경 변화를 동맥압의 변화에 대하여 검정한 결과 혈관이완과 혈관수축의 희귀 직선의 경사도는 10^-5M L-NNA의 전처치에 의하여 영향을 받지 아니하였으나, 3 × 10^-6M glibenclamide에 의해 유의하게 감소되었다. 이러한 결과로 보아 혈압하강에 대해 쥐의 뇌연막동맥에 나타나는 혈관이완반응은 EDRF(NO)에 의해 매개되지 않는다고 사료된다. In anesthetized rats, we examined the possibility that endothelium-derived relaxing factor (EDRF) or nitric oxide (NO) released in response to cholinergic mechanism may contribute to the reflex autoregulation of cerebral blood flow. Suffusion with mock cerebrospinal fluid (CSF), containing acetylcholine (ACh, 10^-9 ~ 10^-6M) evoked concentration-dependent vasodilatation of the resting pial artery (mean, 19.3 ± 1.7μm, n=36), which was significantly inhibited not only by N{\omega}-nitro-L-arginine (L-NNA, 10^-5M) but also by methylene blue (10^-6M) and oxyhemoglobin (10^-6M). The muscarinic receptors in the endothelium of pial artery implicated in the release of EDRF were considered to be M₁ and M₃ subtypes. When suffused with mock CSF containing L-arginine it caused a transient vasodilatation, which was strongly inhibited by LY 83583 (10^-5M), but not by L-NNA (10^-5M). Additionally, both ACh- and L-arginine-induced vasodilation were significantly inhibited by glibenclamide, a specific ATP-sensitive K⁺ channel blocker. On the other hand, changes in pial arterial diameter were plotted as a function of changes in systemic arterial blood pressure. The slopes of regression lines for vasodilation and vasoconstriction were not affected by pretreatment with 10^-5M L-NNA, but significantly reduced by 3 × 10^-6M glibenclamide. Thus it is suggested that the reflex vasodilation of rat pial arteries in response to a transient hypotension is not mediated by EDRF (NO).

카드미늄의 만성적 투여가 신경접합 전.후 α₂-아드레날인 수용체에 의한 반응에 미치는 영향

홍기환(Ki-Whan Hong),임병용(Byung-Yong Rhim),손의동(Uy-Dong Sohn) 대한약리학회 1985 대한약리학잡지 Vol.21 No.1

전기자극에 의한 적출 정관의 수축 또는 뇌척수제거 흰쥐의 심박동수 증가가 카드뮴 장기투여 (매격일 10μ mols, 1회씩 2주간 복강내 주사)로 인하여 대조군에 비하여 현저히 항진되었다. 이러한 전기자극에 의한 반응은 α₂-효현제인 clonidine에 의하여 억제 되었고, 이 억제는 α₂-길항제인 yohimbine 투여로 봉쇄되었다. 나아가 methoxamine에 의한 확장 혈압의 증가는 카드뮴 투여에 의하여 영향을 받지 아니하였으나 clonidine에 의한 증가는 카드뮴 투여에 의하여 억제되었다. 이러한 결과로 보아 카드뮴 장기 노출에 의하여 시납스 전 및 후 α₂-adrenoceptors가 우선적으로 억제되었다고 시사되는 바이다. Either the contraction of isolated was deferens or the increase of heart rate in the pithed rats induced by electrical stimulation was significantly augmented by cadmium administration (10 μmols of cadmium acetate every other day for 2 weeks i.p.). These stimulation-induced responses were diminished by α₂-adrenoceptor agonist, clonidine, and the inhibition was antagonized by yohimbine. Furthermore, the increase in diastolic blood pressure by clonidine was also significantly reduced after cadmium administration, whereas that by methoxamine was not influenced with this dose range of cadmium. With these results it may be postulated that the long-term cadmium exposure may preferentially affect the responsiveness of the presynaptic as well as the postsynaptic α₂-adrenoceptors.

레그호온의 산란유무(産卵有無)에 따른 Adrenergic Receptor의 변동(變動)

홍기환(Ki Whan Hong) 대한약리학회 1977 대한약리학잡지 Vol.13 No.1

The author confirmed the development of the smooth muscle in the oviduct proprius and anterior mesosalpinx in the leghorn, and observed that there was a variation between the action of norepinephrine on albumin-secreting portion of productive oviduct and that of non-productive one, and that PGE₁ might play a significant role on the activation of adrenergic α-receptor in the non-productive oviduct. 1. There were many bundles of smooth muscles with irregular directions, which were identified in the both oviduct proprius and anterior mesosalpinx by Mallory aniline-blue orange G stain. 2. In vitro experiments, the anterior mesosalpinx was always relaxed by norepinephrine. While the albumin-secreting portion of non-productive period of oviduct was relaxed, but that of the productive one contracted by norepinephrine. Both the anterior mesosalpinx and oviduct proprius of chick responsed with relaxation to norepinephrine as shown in the non-productive hen. In vivo experiments, norepinephrine injected through the jugular vein increased the intraoviductal pressure in the productive oviduct, but decreased that in the non-productive one. 3. By treatment with PGE₁, in vitro, the relaxation induced not only by norepinephrine, but by periarterial electrical stimulation was converted into contraction, and in the presence of phentolamine, this conversion by PGE₁ was not shown. 4. The intra-oviductal pressure of the productive hen treated with indomethacin for 4 days was decreased by norepinephrine, but the increase in pressure by PGE₁ or PGE₂ was supersensitized when these drugs were administered through jugular vein. However, in vivo, the relaxation by norepinephrine was not converted into the stimulation after PGE₁ treatment. It might be summarized that the regulation of intra-oviductal pressure was dependent on the summation of the movement of both oviduct and mesosalpinx and intramurally produced prostaglandins contributes to the inherent tone of the prcductive oviduct by activating adrenergic α-receptor.