• 대한약리학회지
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• 제22권1호
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• pp.45-50
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• 1986

후신경구절제(OB) 흰쥐에 있어서 muricide의 발생은 중추성 ${\alpha}$-adrenoceptors의 기능항진과 밀접한 관계가 있다는 가설하에 다음 실험을 행하였다. Muricide를 일으키는 OB 흰쥐의 전뇌내 noradrenaline(NA)의 전환율은 대조군에 비하여 현저히 낮았으나 $_{{\alpha}_2}$-adrenoceptor 길항약물인 yohimbine이나 idazoxan 투여시 NA 전환은 muricide의 억제와 함께 현저히 증가되었다. OB흰쥐의 전뇌 피질막의 $[^3H]$ yohimbine에 대한 최대결합능(Bmax)은 대조군에 비하여 현저히 높았다. ${\alpha}$-Adrenoceptor 효능약물 및 길항약물에 대한 친화도는 아무런 변동이 없었다. 이상의 결과로 보아 OB흰쥐에서 야기되는 muricide는 중추성 ${{\alpha}_2}$-adrenoceptor의 기능 항진과 밀접한 관련이 있다고 사료되는 바이다.

• 한국임상수의학회지
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• 제6권1호
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• pp.199-208
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• 1989

This study was carried out to Investigate the effects of detomidine and xylazine on physical sign, electrocardiogram, blood pressure, acid-base status and the antagonistic effect of yohimbine on detomidine in goats. Yohimbine was administered 10 minutes after detomidine injection. Maintenance time of sedation was remarkably decreased in yohimbine-treated group(59.5${\pm}$3.8min). compared with detomidine-treated group(99.8 ${\pm}$ 14.7min). Body temperature was slightly decreased, heart rate was markedly decreased in all experimental groups and respiratory rate increased in detomidine-treated group and decreased in zylazine-treated group. However they were recovered rapidly after yohimbine administration In electrocardiogram, there were no significant changes except T waves and RR intervals. T waves showed negative form and RR intervals were increased but they were recovered rapidly in yohimbine-treated group compared with detomidine-treated group. Blood pressure was decreased after detomidine administration but recovered faster in yohimbine-treated group than in detomidine alone group. Blood pH was increased in detomidine-treated and yohimbine-treated groups but unchanged in xylazine-treatd group. It is considered that the effects of detomidine are similar to those of xylaxine and yohimbine is effective antagonist to detomidine in goats.

• Archives of Pharmacal Research
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• 제23권4호
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• pp.353-359
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• 2000

${\alpha}_2$-Adrenoceptor antagonists, which can enhance synaptic norepinephrine levels by blocking feedback inhibition processes, are potentially useful in the treatment of disease states such. as depression, memory impairment, impotence and sexual dysfunction. (10bS)-1,2,3,5,6,10b-Hexahydropyrrolo[2,1-a]isoquinoline oxalate (YSL-3S) was evaluated in several in vitro biological tests to establish its pharmacological profile of activities as an ${\alpha}_2$-adrenoceptor antagonist. Saturation binding assay revealed that$^{3}[H]$rauwolscine bound to the $\alpha$$_2$-adrenoceptors with a Kd value of 6.3$\pm$0.5 nM and a Bmax value of 25l$\pm$39 fmol/mg protein in rat cortical synaptic membranes. Competitive binding assay showed that YSL-3S inhibited the binding of$^3[H]$rauwolscine (1 nM) in a concentration-dependent manner with a Ki value of 98.2$\pm$12.1 nM while it did not inhibit the binding of [$^3$H]cytisine (1.25 nM) to neuronal nicotinic cholinergic receptors. The Ki values of yohimbine, clonidine and norepinephrine for $^3[H]$rauwolscine binding were 15.8$\pm$1.0, 40.1$\pm$5.9 and 40.0$\pm$11.5 nM, respectively. In addition, the binding affinity of YSL-3S for ${\alpha}_2$-adrenoceptors was higher than that of its antipode and the racemic mixture. The functional activity of YSL-3S at the presynaptic ${\alpha}_2$-adrenoceptors was assessed using the prostatic portion of the rat vas deferens. Clonidine inhibited field-stimulated contractions of the vas deference in a dose-dependent manner. The presence of YSL-3S or yohimbine caused a parallel, rightward the dose-response curve of clonidine in a dose-dependent manner, indicating an antagonistic action at the presynaptic ${\alpha}_2$-adrenoceptors. The $pA_2$values of yohimbine and YSL-3S were 7.66$\pm$0.13 and 6.64$\pm$0.18, respectively. The results indicate that YSL-3S acts as a competitive antagonist at presynaptic ${\alpha}_2$ -adrenoceptors with a potency approximately ten times lower than yohimbine, but is devoid of binding affinity for neuronal nicotinic cholinergic receptors.

• 한국어병학회지
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• 제14권1호
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• pp.31-36
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• 2001

해수에 적응된 뱀장어, Anguilla japonica의 장 세포막으로부터 새로운 clonidine의 결합부위가 있음이 밝혀졌다. Clonidine의 특이적인 결합부위는 적어도 2개의 부위 (high affinity $K_d=1.4{\pm}0.3$ nMn= 5, low affinity $K_d=175{\pm}34$ nM)를 가지고 있었다. 2nM [$^3H$]clonidine의 특이적인 결합은 $20^{\circ}C$, pH 7.5에서 최적 결합능을 가지고 있었고, 라벨되지 않은 clonidine에 의해 가역적인 반응을 보였다. 이러한 결합은 adrenaline, yohimbine과 rauwolscine에 의한 저해능은 약하였다. 그리고 대부분의 결합부위는 $\alpha_2$-adrenoceptor와는 상이하였다. Clonidine의 특이적인 결합은 다양한 imidazoline/guanidinium약물에 의해 억제되었다. Competition 실험의 결과, 2nM[$^3H$]clonidine의 치환 rank order는 다음과 같다. guanabenz > cirazoline = naphazoline=UK14,304= ST587 $\geq$ clonidine $\geq$ idazoxan = RX821002 = tolazoline > ST93 = oxymetazoline = amiloride = ST91 > yohimbine = efaroxan = rauwolscine $\geq$ adrenaline = ST567 = histamine = agmatine. 이러한 순서는 포유류에 분류된 imidazoline receptorl($I_1$), imidazoline receptor 2($I_2$) 및 imidazoline/guanidinium receptive sites(IGRS)형태와는 틀리기 때문에 새로운 imidazoline receptor라고 생각된다. 지금까지 보고된 포유류의 세포와 조직에서 IGRS의 생리학적인 역할은 명확하지 않지만, 해수뱀장어 장은 IGRS의 세포에 있어서의 역할 그리고 IGRS의 내인성(內因性) ligand가 무엇인가에 대한 좋은 모델이 될 수 있다고 생각되어진다.

• 대한수의학회지
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• 제33권1호
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• pp.71-80
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• 1993

The central nervous system depressant effect of xylazine and xylazine-ketamine was studied in chicken and mice. Intraperitoneal injection of xylazine(1~30 mg/kg) and xylazine(1~30 mg/kg)-ketamine(100 mg/kg) induced a loss of the righting reflex in chicken and mice, respectively. These effects of xylazine were dose-dependent. The results obtained were as follows; 1. The effect of xylazine-induced depression was antagonized by adrenergic antagonists having ${\alpha}_2$-blocking activity(yohimbine, tolazoline, piperoxan and phentolamine). 2. Yohimbine was most effective in the reduction of the CNS depression by xylazine. 3. Phenoxybenzamine and prazosin did not reduced CNS depression by xylazine in both species. 4. Labetalol (${\alpha}_1$, ${\beta}_1$-adrenergic antagonist) and propranolol(${\beta}$-adrenergic blocking agent) were not effective in reducing xylazine induced depression. 5. Cholinergic blocking agents (atropine and mecamylamine), a dopaminergic antagonist (Haloperidol), a histamine $H_1$-antagonist(chlorpheniramine), a histamine $H_2$-antagonist(cimetidine), a serotonergic-histamine $H_1$ antagonist(cyproheptadine) were not effective in reducing xylazine-induced depression. 6. Xylazine-induced depression is mediated by ${\alpha}_2$-adrenergic receptors and appears not to be involved in cholinergic, dopaminergic, serotonergic or histaminergic pathways.

• 셀메드
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• 제2권4호
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• pp.38.1-38.6
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• 2012

The present study aimed to determine the possible mechanisms of the peripheral antinociception of the aqueous extracts of Dicranopteris linearis (AEDL), Melastoma malabathricum (AEMM) and Bauhinia purpurea (AEBP) leaves in mice. Briefly, the antinociceptive profile of each extract (300, 500, and 1000 mg/kg; subcutaneous (s.c.)), was established using the abdominal constriction test. A single dose (500 mg/kg) of each extract (s.c.) was pre-challenged for 10 min with various pain receptors' antagonists or pain mediators' blockers and 30 min later subjected to the antinociceptive assay to determine the possible mechanism(s) involved. Based on the results obtained, all extracts exerted significant (p < 0.05) antinociceptive activity with dose-dependent activity observed only with the AEMM. Furthermore, the antinociception of AEDL was attenuated by naloxone, atropine, yohimbine and theophylline; AEMM was reversed by yohimbine, theophylline, thioperamide, pindolol, reserpine, and 4-chloro-DL-phenylalanine methyl ester hydrochloride; and of AEBP was inhibited by naloxone, haloperidol, yohimbine and reserpine. In conclusion, the antinociceptive activity of those extracts possibly involved the activation of several pain receptors (i.e. opioids, muscarinic, ${\alpha}_2$-adrenergic and adenosine receptors, adenosine, H3-histaminergic and $5HT_{1A}$, dopaminergic receptors).

• 대한약리학회지
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• 제23권2호
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• pp.123-131
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• 1987

Morphine을 비롯한 opioid peptide가 말초 또는 중추에 투여시 혈압하강과 심박동수감소를 보이며 opiate 수용체 길항제인 naloxone에 의해 길항됨이 관찰되었던바 근래 몇몇 보고들은 중추신경내에서 adrenergic및 opioidergic system이 서로 관련되어 있음을 시사하고 있다. 이에 본 실험에서 고혈압 연구에 널리 사용되고 있는 2-kidney, 1-clip (2K1C) 방법으로 실험적 고혈압을 유발시킨 백서의 측뇌실내 clonidine또는 morphine의 심맥관계에 대한 효과와 각각의 차단제에 의한 영향 그리고 정상 및 고혈압상태 백서의 뇌내 ${\beta}-endorphin$의 함량과 specific opiate receptor binding을 정량하여 고혈압 유발에 따른 뇌내 opiate system의 변동을 관찰하였다. 2K1C 고혈압 또는 sham-operated대조백서에서 측뇌실내 clonidine $(3-30\;{\mu}g/kg)$은 용량에 비례하여 혈압하강과 심박동수감소를 일으켰으며 clonidine의 혈압강하 효과는 2K1C고혈압 백서에서 더욱 현저하였다. clonidine의 혈압강하효과는 고혈압 백서에서 측뇌실내 yohimbine 또는 naloxone 전처리에 의해 약화되었고 대조군에서는 yohimbine ($30\;{\mu}g/kg$, i.v.t.)에 의해 억제되었으나 naloxone ($50\;{\mu}g/kg$, i.v.t.)에 의해서는 영향 받지 않았다. clonidine과 마찬가지로 측뇌실내 morphine $(10-100\;{\mu}g/kg)$은 2K1C 고혈압 또는 sham-operated 대조백서에서 용량에 비례하여 혈압하강과 심박동수감소를 일으켰으며, morphine의 혈압강하효과는 2K1C 고혈압백서에서 더욱 현저하였다. 대조군과 고혈압군에서 morphine의 혈압강하효과는 naloxone 전처리에 의해 현저히 약화되었으나 yohimbine에 의해서는 영향 받지 않았다. 2K1C 시술익일부터 투여한 clonidine은 2K1C 시술에 의한 혈압 상승을 억제하였으며 naloxone (2 mg/kg, i.p.)에 의해 반전되었다. 2K1C 시술에 의해 고혈압이 유발된 백서의 뇌내 ${\beta}-endorphin$ 함량은 sham-operated 군에 비하여 유의하게 감소되어 있었고 (3H)-naloxone의 specific binding의 Bmax는 증가되었으나 Kd치는 변동되지 않았다. 이상의 실험 성적은 뇌내 opiate계가 혈압조절에 중요한 역할을 담당하고 있으며 2K1C 고혈압백서의 고혈압상태 유지에 뇌내 opiate계의 기능저하가 일부관여하고 있음을 강력히 시사한다.

• The Korean Journal of Physiology and Pharmacology
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• 제1권5호
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• pp.485-493
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• 1997

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.

• Biomolecules & Therapeutics
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• 제19권3호
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• pp.315-319
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• 2011

Galanin (Gal) is a 29-amino-acid neuropeptide which is expressed in superior cervical ganglion (SCG) neurons and plays a trophic role in the adult animal and acts as an inhibitory modulator of cholinergic and noradrenergic neurotransmission. Whether activation or inhibition of alpha-adrenoreceptors infl uences Gal mRNA expression in SCG neurons remains unknown. Here, we have evaluated the possible regulation of Gal mRNA expression with acute (4 h) and chronic (4 days) stimulation of alpha 1- and alpha 2-adrenoreceptor agonists or antagonists in primary cultured SCG neurons. The results showed that the amount of Gal mRNA expression in cultured SCG neurons increased signifi cantly after chronic stimulation with alpha 2-adrenoreceptor antagonist yohimbine compared with control SCG neurons at the same time point, whereas the amount of Gal mRNA expression decreased signifi cantly after chronic stimulation with alpha 2-adrenoreceptor agonist clonidine as compared with that in control group. All these effects were not dose-dependent on the administration of alpha 2-adrenoreceptor agonist clonidine or alpha 2-adrenoreceptor antagonist yohimbine. Alpha 1-adrenoreceptor agonist phenylephrine or antagonist prazosin chronic stimulation did not have effects on Gal mRNA expression. Acute exposure of these agents did not have effects on Gal mRNA expression. The present study showed that Gal may be regulated by activation or inhibition of alpha 2-adrenoreceptors, but not alpha 1-adrenoreceptors in sympathetic neurons.

• 대한약리학회지
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• 제20권2호
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• pp.15-21
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• 1984

Clonidine으로 고혈압을 치료시 부작용으로 진정작용이 심하게 나타나며 이는 Clonidine이 중추 ${\alpha}_2$-수용체를 흥분시켜서 일으킨 결과임이 보고되었다. 본 실험에서는 부화 $1{\sim}2$일이 된 병아리에 ${\alpha}_2$-수용체 효현제들을 주사하여 정좌반사가 소실될 때까지의 시간 및 수련시간을 관찰하였으며, 그리고 guanabenz 유도 수면에 대한 ${\alpha}_1$- 및 ${\alpha}_2$-수용체 길항제 및 opiate수용체 길항제가 어떻게 관여하는 지를 검토하고 다음과 같이 요약하였다. 1) ${\alpha}_2$-수용체 효현제중 guanabenz, clonidine, guanfacine 및 B-HT 933은 용량에 의존해서 정좌반사소실까지의 잠복시간을 감소시켰다. 그러나 B-HT 920 및 oxymetazoline은 잠복시간을 경미하게 연장시켰다. 2) ${\alpha}_2$-수용체 효현제들은 용량에 비례해서 수면시간을 증가시켰고 이들의 강도는 guanabenz>clonidine>oxymetazoline${\geq}$B-HT 933${\geq}$B-HT 920> guanfacine의 순위이었다. 3) ${\alpha}_2$-수용체 길항제들은 양에 비례해서 guanabenz 유도 수면시간을 감소시켰으며 이들의 강도는 yohimbine>rauwolscine>piperoxan${\geq}$RX 781094의 순위 이었다. 4) Ethanol 및 hexobarbital유도 수면은 yohimbine에 의해 봉쇄되지 아니하였다. 5) Guanabenz유도 수면시간에 대해서 ${\alpha}_1$-수용체 효현제인 methoxamine 및 Phenylephrine은 영향이 없었으나, ${\alpha}_1$-수용체 결항제인 Prazosin은 증가시켰다. 그러나 corynanthine은 반대로 수면시간을 현저히 감소시켰다. 이상의 결과로 보아 중추 ${\alpha}_2$-수용체의 흥분으로 병아리의 수면이 야기되고, 중추 ${\alpha}_1$-수용체의 역할에 대하여는 명백하지 않으나 ${\alpha}_2$-수용체 효현제 및 길항제의 성질을 규명하는 동물모델로서 부화 I${\sim}$2일의 병아리가 크게 유용할 것으로 시사되는 바이다.