• 대한약리학회지
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• 제21권1호
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• pp.27-33
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• 1985

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.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.323-330
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• 1998

Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethylamines. Many of them, especially with 6,7-disubstitution, demonstrate a relatively high affinity for catecholamines. Present study examines the pharmacological action of limited series of THI, using rats' isolated atria and aorta. In addition, a $[^3H]$ prazosin displacement binding study with THI compounds was performed, using rat brain homogenates to investigate whether these probes have ?${\alpha}$-adrenoceptor affinity. We also compared the vascular relaxation potency of these probes with dobutamine. YS 49, YS 51, higenamine and dobutamine, concentration-dependently, relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ${\mu}M$) in which $pEC_{50}$ were $5.56{\pm}0.32$ and $5.55{\pm}0.21$, $5.99{\pm}1.16$ and $5.57{\pm}0.34$, respectively. These probes except higenamine also relaxed KCl (65.4 mM)-contracted aorta. In isolated rat atria, all THIs and dobutamine increased heart rate and contractile force. In the presence of propranolol, the concentration response curves of YS 49 and YS 51 shifted to the right and resulted in $pA_2$ values of $8.07{\pm}0.84$ and $7.93{\pm}0.11$, respectively. The slope of each compound was not deviated from unity, indicating that these chemicals are highly competitive at the cardiac ?${\beta}-adrenoceptors$. YS 49, YS 51, and higenamine showed ?${\alpha)-adrenoceptor$ affinity in rat brain, in which the dissociation constant $(K_i)$ was 2.75, 2.81, and 1.02 ${\mu}M$, respectively. It is concluded, therefore, that THI alkaloids have weak affinity to ${\alpha)_1-adrenoceptor$ in rat aorta and brain, respectively, while these probes show relatively high affinity for cardiac ${\beta}-adrenoceptors$. Thus, these chemicals may be useful in the treatment of congestive heart failure.

• Journal of Acupuncture Research
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• 제22권1호
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• pp.99-108
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• 2005

Collagen 유발(誘發) 관절염(關節炎) 동물모델을 이용하여 족삼리(足三里) (ST36) 봉독약월(蜂毒藥鉞)의 진통효과(鎭痛效果)와 그 기전(機轉) 을 관찰하기 위하여 TFL을 지표로 하여 통증 역치의 변화와 naloxone 및 yohimbine으로 전처(前處) 치한(置) 후 (後) 봉독약침(蜂毒藥鍼)의 진통효과(鎭痛效果)를 관찰한 결과 다음과 같은 결론을 얻었다. 1. Collagen 유발(誘發) 관절염(關節炎)의 rat에서 TFL 통증 역치는 1, 2, 3 및 4주로 갈수록 지속적 감소를 나타내었다. 2. 1회와 2주간 봉독약철(蜂毒藥鐵)은 collagen 유발(誘發) 관절염(關節炎) rat의 통증역치를 각각 증가시켰다. 3. CIA rat에 opioid receptor antagonist인 naloxone을 투여한 후 봉독약침(蜂毒藥鍼)을 처치한 결과 진통효과(鎭痛效果)가 유지되는 것으로 보아 봉독약광(蜂毒藥鑛)의 진통기전(鎭痛機轉)은 아편양 기전(機轉)과 관련이 없는 것으로 사료된다. 4. CIA rat에 ${\alpha}2$-adrenoceptor antagonist인 ohimbine을 투여한 후 봉독약침(蜂毒藥鍼)을 처치한 결과 진통효과(鎭痛效果)가 길항(拮抗)되는 것으로 보아, 봉독약침(蜂毒藥鍼)의 기전(機轉)은 ${\alpha}2$-adrenoceptor에 의하여 매개는 것으로 사료된다.

• 대한약리학회지
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• 제22권2호
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• pp.115-122
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• 1986

Urethane 마취 가토에서 뇌내 alpha-1및 alpha-2 adrenoceptor의 작용에 미치는 calcium antagonist의 영항을 알아보고자 뇌실내 methoxamine과 clonidine의 혈압및 심박수 변동에 미치는 diltiazem, nifedipine의 영향을 조사한 결과, 1). 뇌실내 methgramine(1mg)은 혈압상승및 심박수 감소를 일으켰고, 뇌실내 clonidine$(30{\mu}g)$은 혈압하강및 심박수 감소를 일으켰다. 2). 뇌실내 diltiazem과 nifedipine은 dose-dependent한 혈압하강을 일으켰으며 심박수 감소를 일으켰다. Diltiazem에 비하여 nifedipine은 혈압하강 효과는 크고 심박수 감소효과는 작았다. 뇌실내 diltiazem$(400{\mu}g)$, nifedipine$(35{\mu}g)$의 혈압하강 작용은 완만하고 지속적이었으나 같은 양의 정맥내 투여효과는 일과성이었다. 3). 뇌실내 diltiazem$(400{\mu}g)$이나 nifedipine$(35,\;350{\mu}g)$ 처리 후에 methoxamine(1mg)의 혈압상승 효과는 영향받지 않았으나 심박수감소 효과는 유의하게 감약되었다. 4). Clonidine의 혈압하강 작용은 뇌실내 diltiazem$(400{\mu}g)$이나 nifedipine$(35,\;350{\mu}g)$ 처리 후에 감약되었으나 정맥 내 diltiazem$(200{\mu}g/kg)$이나 nifedipine$(30{\mu}g/kg)$ 후에는 영향받지 않았다. Clonidine의 심박수 감소작용은 .뇌실내및 정맥내 diltiazem이나 nifedipine 처리후에 감약되었다. 5). 뇌실내 clonidine$(30{\mu}g)$ 처 리후 뇌실내 diltiazem$(400{\mu}g)$과 nifedipine$(350{\mu}g)$의 혈압하강및 심박수 감소효과는 영향 받지 않고 그대로 나타났다. 이상의 결과로 diltiazem과 nifedipine은 가토뇌내에서 methoxamine에 의한 혈압상승의 작용점인 alrfia-1 adrenoceptor의 흥분에는 영향을 미치지 못하나 clonidine의 작용점인 alpha-2 adrenoceptor의 흥분에 의한 혈압하강및 심박수 감소효과는 억제한다고 추론하였다.

• 대한약리학회지
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• 제32권2호
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• pp.189-199
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• 1996

Myocardial ${\alpha}_1-adrenoceptors$ have been shown to mediate a biphaslc inotropic response that was characterized by a transient decline followed by a sustained increasing phase in guinea pig ventricular muscle. Recently one group reported that an ${\alpha}_1-adrenoceptors-induced$ intracellular $Na^+$ decrease is linked to fast $Na^+$ channel inhibition and another group reported that it is linked to $Na^+$-$K^+$ pump activation by ${\alpha}_{1b}-adrenoceptors$. But until now, its mechanism is not clear. Therefore, to see whether the $Na^+$channel or $Na^+-K^+$ pump is related to a decrease in intracellular $Na^+$ activity and/or the negative inotropic response, and which ${\alpha}_1-adrenoceptor$ subtype was involved in the decrease in intracellular $Na^+$activity by phenylephrine, we used conventional and sodium selective microelectrodes, and tension transducer to determine the effects of ${\alpha}_1-adrenergic$ stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force in guinea pig ventricular muscles. $10^{-5}$ M Phenylephrine produced a slight hyperpolarization of the diastolic membrane potential, a decrease or increase in $a_N^i_a$, and a biphasic inotropic response. The negative inotropic response accompanied by a decrease in intracellular $Na^+$activity, whereas in muscles showing a remarkable positive inotropic response without initial negative inotropic effect was accompanied by an increase in intracellular $Na^+$ activity. The decrease in intracellular $Na^+$ activity was apparently inhibited by WB4101, an antagonist of the ${\alpha}_{1a}-adrenoceptors$. The decrease in intracellular $Na^+$ activity caused by phenylephrine was not abolished or reduced by a block of the fast $Na^+$ channels. $V_{max}$ also was not affected by phenylephrine. Phenylephrine produced an increase in intracellular $Na^+$ activity in the presence of a high concentration of extracellular $Ca^{2+}$ (in quiescent muscle) or phorbol dibutyrate, a protein kinase C activator(in beating muscle). These suggest that the ${\alpha}_{1a}-adrenoceptors-mediated$ decrease in intracellular $Na^+$ activity may be related to the protein kinase C.

• 약학회지
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• 제32권4호
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• pp.258-273
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• 1988

In this study attempts were made to observe the effects of guanabenz on renal function in dog, which manifests the antihypertensive action by inhibition of sympathetic tone through stimulating the presynaptic adrenoceptor (${\alpha}_2-adrenoceptor$). Guanabenz, when injected at a dose of $30.0{\mu}g/kg$, or infused at a dose of $3.0{\mu}g/kg/min$ intravenously, produced diuretic action with increased amounts of $Na^+\;and\;K^+$ in urine, and with decreased reabsorption rates of $Na^+\;and\;K^+$ in renal tubules. It was also observed that the rates of osmolar and free water clearances were increased, but the glomerular filtration rate and renal plasma flow were not changed. Guanabenz injected at a dose of $3.0{\mu}g/kg$ into a carotid artery or infused intravenously at a dose of $3.0{\mu}g/kg/min$ in a state of water diuresis elicited the diuretic action of the similar aspect as a case of guanabenz given intravenously. The diuretic action produced by guanabenz was completly blocked by pretreatment of i.v. prazosin, ${\alpha}_1-adrenoblocking$ agent, or of i.v. yohimbine, ${\alpha}_2-adrenergic$ blocking agent. Prazosin, when given into a renal artery, inhibited the diuretic action by i.v. guanabenz in only injected kidney, whereas in case of yohimbine the action was inhibited in both kidney. Guanabenz infused at a dose of $1.0{\mu}g/kg/min$ into a renal artery exhibited no significant changes of renal function in both kidney. In denervation experiments, guanabenz given intravenously produced typical diuretic action in innervated kidney, whereas in denervated kidney, it did not affect the action at initial period but exhibited the action with increase of only free water clearance at later period. These results suggest that guanabenz produced diuretic action in dog by inhibition of electrolyte reabsorption rates in renal tabules, mainly proximal tubule and of ADH release, which is mediated by stimulating of central sympathetic ${\alpha}_2-receptor$.

• 대한약리학회지
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• 제19권1호
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• pp.123-131
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• 1983

1) Urethane 마취가토(痲醉家兎)에서 경뇌막외강내(硬腦膜外腔內)에 삽입(揷入)한 balloon을 통(通)한 가압(加壓) 및 두개내압기종방법(頭蓋內壓記種方法)에 의하여 내압(內壓)을 상승(上昇)시키고, 이 내압상승(內壓上昇)에 따른 혈압상승(血壓上昇)에 미치는 ${\alpha}_2-adrenoceptor$ antagonist인 yohimbine의 영향(影響)을 관찰(觀察)하였다. 2) 내압(內壓)은 가압(加壓)balloon 내(內) 식염수주입(食鹽水注入)으로 주입초기(注入初期) 에는 완만(緩慢)하게 그 후 점차(漸次) 급격(急激)하게 상승(上昇)하였다. 이에 따라 혈압(血壓)은 처음에 경미(輕微)한 하강경향(下降傾向)을 보인 후 급격(急激)하게 상승(上昇)하였고, 더욱 내압(內壓)을 상승(上昇)시키면 혈압(血壓)은 심(甚)한 하강(下降)을 보였다. 최고혈압상승정도(最高血壓上昇程度)는 원혈압(元血壓)의 $49{\pm}2.4%$(32예(例) 평균(平均)${\pm}SE)$의 증가(增加)였으며, 이때에 가압(加壓)balloon 내(內)로 주입(注入)된 식염수양(食鹽水量)은 $1.22{\pm}0.15\;ml$, 내압(內壓)은 $165{\pm}6.4\;mmHg$였다. 3) 측뇌실내(側腦室內) yohimbine$(50{\mu}g)$은 혈압자체(血壓自體) 영향(影響)을 미치지 못하였으나, 본양(本量)의 yohimbine 투여후(投與後)에는 가압(加壓)balloon내(內)에 대조동물(對照動物)에서보다 훨씬 적은 양(量)의 식염수주입(食鹽水注入)으로 내압(內壓) 및 혈압(血壓)이 상승(上昇)하였다. 즉(卽) 최고혈압상승(最高血壓上昇) (6예평균(例平均, $57{\pm}4.5%)$이 나타날 때의 가압(加壓)balloon 내(內)에 주입된 식염수양(食鹽水量)은 $0.83{\pm}0.02\;ml$, 내압(內壓)은 $164{\pm}9.6\;mmHg$였다. 4) $Clonidine(30\;{\mu}g)$의 측뇌실내(側腦室內) 주입후(注入後) 혈압자체(血壓自體)는 하강(下降)되었고 이때 가압(加壓)balloon 내 식염수주입(食鹽水注入)에 의한 내압상승(內壓上昇)은 대조군(對照郡)보다 순화(純化)되었으며 혈압상승(血壓上昇)은 거의 볼 수 없었다. 5) $Clonidine(30\;{\mu}g)$투여(投與)로 하강(下降)된 혈압(血壓)은 $yohimbine(500\;{\mu}g)$투여(投與)로 거의 원혈압(原血壓)으로 회복(回復)되었고, 이때 내압(內壓)을 상승(上昇)시키면 대조군(對照郡)에서와 같은 내압상승(內壓上昇)에 따른 혈압상승(血壓上昇)이 나타났다. 6) 본실험(本實驗) 성적(成績)은 가토(家兎)에서 ${\alpha}_2-adrenoceptor$ antagonist가 뇌(腦)에 존재(存在)할 때는 두개뇌압상승(頭蓋腦壓上昇)에 따른 혈압상승(血壓上昇)이 촉진(促進)되고 또한 ${\alpha}_2-adrenoceptor\;agonist$에 의한 두개뇌압상승(頭蓋腦壓上昇)에 따른 혈압상승(血壓上昇)의 억제(抑制)가 나타나지 않음을 가리키고 있다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.216-216
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• 1996

The purpose of the present study was to determine whether in vivo noradrenergic neural activity in the locus coeruleus is related to the development of hypertension. Two groups of animals were prepared, 1) young spontaneously hypertensive rats (SHR) and 2) age-matched normotensive wistar kyoto rats (WKY). At il weeks of age, the release of norepinephrine (NE) and 3,4-dihydroxyphenylglycol (DOPEG) from locus coeruleus of young SHR and WKY as an index of neural activity were determined by in vivo microdialysis along with blood pressure (BP) at three conditions : 1) normal; 2) elevated BP by systemic injection of phenylephrine and 3) alpha-1 adrenoceptor stimulated by perfusion of phenylephrine into the locus coeruleus through microdialysis probe. Basal releases of NE and DOPEG from the iocus coeruleus were 0.415+/-0.089pg/20min, 1.311+/-0.293 pg/20min in SHR and 0.204+/-0.078 pg/20min, 1.492+/-0.365 pg/20min in WKY respectively. Basal release of NE from the locus coeruleus of SHR was significantly greater than that of WKY. Phenylephrine systemic injection caused elevation of BP in both SHR and WKY in a dose related manner. Following phenyephrine injection, the releases of NE and DOPEG from the locus coeruleus of SHR were significantly decreased, whereas there were no significant changes in the releases of NE and DOPEG In young WKY. Alpha-1 adrenoceptor stimulation in the locus coeruleus by perfused phenylephrine through microdialysis probe caused pressor responses in both SHR and WKY, but the magnitude of pressor response in SHR was larger compared with that in WKY. The result from the present study suggests that noradrenergic neural activity in locus coeruleus may contribute as one of triggering factors for the expression of hypertension in young SHR.

• 대한수의학회지
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• 제28권1호
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• pp.23-28
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• 1988

To examine the selectivity of diltiazem, used in the cardiovascular diseases, on alpha-1 and alpha-2 adrenoceptor-induced pressor responses, effect of diltiazem on alpha-adrenocepter agonist-induced pressor responses were investigated in urethane-anesthetized rabbits and spinal rabbits. The results are summarized as follows: 1. Intravenous diltiazem(10, 30, 100, 300, $1000{\mu}g/kg$) produced dose-dependent depressor response in rabbits. 2. Pressor responses to intravenous norepinephrine($10{\mu}g/kg$) and phenylephrine ($30{\mu}g/kg$) were inhibited by pretreatment with intravenous diltiazem in rabbits and no difference was noted between the degree of both inhibitions of the pressor response by diltiazem. 3. Presser responses to intravenous norepinephrine ($3{\mu}g/kg$), phenylephrine ($20{\mu}g/kg$) and clonidine ($300{\mu}g/kg$) were inhibited by pretreatment with intravenous diltiazem in spinal rabbits. No difference was noted between the inhibition of norepinephrine-induced pressor response and that of phenylephrine-induced pressor response by diltiazem. The inhibition of clonidine-induced pressor response by diltiazem was slightly prominent than that of norepinephrine- or phenylephrine-induced pressor response. These results suggest that diltiazem significantly inhibits both pressor responses mediated by alpha-1 and alpha-2 adrenoceptors.

• 대한수의학회지
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• 제34권3호
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• pp.479-486
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• 1994

Effects of catecholamines and the site of receptor of catecholamines were investigated in the longitudinal muscle of the rumen. In order to this experiment, specimens were obtained from 35 Korean Native Cattles, 2-3 years old, in the Kwang-ju area slaughterhouse. Longitudinal muscle strips of rumen were made from sample, and then measured the isometric contraction with physiograph in $37{^{\circ}C}$ organ bath. The results were summarized as follows. 1. 30% of all strips showed rhythmic contraction after short incubation time. 2. Relaxation produced by catecholamines in this preparations increased in a dose-dependant manner. 3. Isoproterenol(${\beta}$-agonist) caused relaxation, but phenylephrine(${\alpha}_1$-agonist) and xylazine(${\alpha}_2$-agonist) were unaffected. 4. The relaxation induced by epinephrine and norepinephrine were not affected by phentolamine(${\alpha}$-blocker) and prazosin(${\alpha}_1$-blocker), yohimbine(${\alpha}_2$-blocker). But propranolol(${\beta}$-antagonist) abolished the effect of catecholamines on relaxation. 5. It is concluded that catecholamines produced relaxation in the longitudinal muscle of rumen via the ${\beta}$-adrenoceptor.