• 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.

• 대한약리학회지
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• 제18권2호
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• pp.59-67
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• 1982

1) 여러가지 말초(末梢) 조직(組織)에서 ${\alpha}_1-adrenoceptor$의 agonist로 알려져 있는 oxymetazoline의 측뇌실내(側腦室內) 투여(投與)는 urethane마취가토(麻醉家兎)의 혈압상승(血壓上昇)을 일으켰다. 이 상승(上昇)은 guanethidine, chlorisondamine처리(處理)로 거의 영향(影響)을 받지 않았고, phenotolamine, guanethidine과 chlorisondamine 또는 부신결찰(副腎結紮)과 guanethidine처리하(處理下)에서는 억제(抑制)되었다. 2) 측뇌실내(側腦室內) oxymetazoline에 의한 혈압상승(血壓上昇)은 측뇌실내(側腦室內) prazosin투여후(投與後)에는 현저(顯著)히 감약(減弱)되었으나 yohimbine 및 piperoxan의 영향(影響)은 받지 않았다. 3) Reserpine처리(處理) 가토(家兎)에서도 측(側) 뇌실내(腦室內) oxymetazoline은 혈압(血壓) 상승(上昇)을 일으켰으며, 이도 측(側) 뇌실내(腦室內) prazosin투여후(投與後)에는 현저(顯著)히 감약(減弱)되었으나 yohimbine의 영향(影響)은 받지 않았다. 4) 전신마취(全身麻醉) 가토(家兎) 및 척수가토(脊髓家兎)에서 정맥내(靜脈內) oxymetazoline은 혈압상승(血壓上昇)을 일으켰으며 이 상승효과(上昇效果)에 대(對)한 정맥내(靜脈內) ${\alpha}_1-adrenoceptor$ antagonist의 길항능력(拮抗能力)은 prazosin, phentolamine, yohimbine의 순(順)으로 강(强)하였다. 5) 본(本) 실험성적(實驗成績)은 oxymetazoline이 혈압조절(血壓調節)에 관여(關與)하는 가토(家兎) 뇌조직(腦組織) 및 가토(家兎) 혈관근(血管筋)에서는 ${\alpha}_1-adrenoceptor$ agonist로 작용(作用)함을 가리키고 있다.

• 대한약리학회지
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• 제21권2호
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• pp.90-98
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• 1985

새앙쥐 강제수영 실험에서 부동자세 시간의 단축은 향주도성 행동의 항진이라는 본능적 충동의 유발이라는 가정 아래 중추 noradrenaline neuron에 있어서 ${\alpha}_1$- 및 ${\alpha}_2$-adrenoceptor의 역할과 관련지어 이 실험을 행하였고 다음과 같은 결론을 얻었다. 1. 새앙쥐를 이용한 강제수영 실험에서 부동자세 시간은 clonidine 및 guanabenz 등과 같은 ${\alpha}_2$-agonists에 의하여 용량에 의존하여 단축되었다. B-HT 933 및 oxymetazoline은 용량에 의존하지 않으나 단축시켰다. xylazine에의하여는 오히려 증가되었다. 2.${\alpha}_1$-Agonists 인 cirazoline, amidephrine 및 methoxamine은 부동자세 시간에 일관성 있는 영향을 미치지 아니하였다. 3. Clonidine과guanabenz에 의한 부동자세 시간의 단축은 ${\alpha}_2$-antagonists, yohimbine, idazoxan 및 phentolamine 전처치로 봉쇄되었으나 ${\alpha}_1$-antagonists, prazosin 및 corynanthine에 의하여는 영향을 받지 아니하였다. 4, d-Amphetamine 투여시 부동자세 시간은 용량에 비례하여 단축되었고, 이러한 단축효과는 yohimbine에 의하여는 길항되었으나 prazosin에 의하여는 영향을 받지 아니하였다. 5. ${\alpha}$-methyl-p-tyrosine 이나 reserpine 또는 두 약물을 동시에 전처치 하였을때 clonidine에 의한 부동자세 시간의 단축은 영향을 받지 아니하였다. 6. Desipramine 및 imipramine 같은 항우울제를 장기처치 또는 장기간 저기충격 요법을 가한 새앙쥐에서도 clonidine의 효과는 영향을 받지 아니하였다. 이상의 결과로 보아 새앙쥐의 강제수영 실험에서의 부동자세 시간의 변동은 중추내 noradrenergic neuron의 postsynaptic ${\alpha}_2$-adrenoceptor와 밀접한 관련이 있다고 시사되며 이러한 ${\alpha}_2$-agonists에 의하여 항진되는 escape-directed behavior는 자기보호를 위한 일종의 충동의 유발로 인한 행동으로 사료된다.

• 대한수의학회지
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• 제38권1호
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• pp.29-42
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• 1998

$Mg^{2+}$ is one of the most abundant divalent cations in mammalian body(0.2~1.0mM) and the important physiological roles are : first, the cofactor of many enzyme activities, second, the regulator of glycolysis and DNA synthesis, third, the important role of bioenergetics by regulating of phosphorylation, fourth, the influence of cardiac metabolism and function. In this work we have investigated the regulation of the $Mg^{2+}$ induced by ${\alpha}_1-adrenoceptor$ stimulation in perfused guinea pig hearts and isolated myocytes. The $Mg^{2+}$ content of the perfusate or the supernatant was measured by atomic absorbance spectrophotometry. The elimination of $Mg^{2+}$ in the medium increased the force of contraction of right ventricular papillary muscles, and the left ventricular pressure. Phenylephrine also enhanced the force of contraction in the presence of $Mg^{2+}-free$ medium. ${\alpha}_1-Agonists$ such as phenylephrine and methoxamine were found to induce $Mg^{2+}$ efflux in both perfused hearts and myocytes. These effects were blocked by prazosin, an ${\alpha}_1-adrenoceptor$ antagonist. The $Mg^{2+}$ influx could also be induced by phenylephrine and R59022, a diacylglycerol kinase inhibitor. In the presence of protein kinase C(PKC) inhibitors, phenylephrine produced an increase in $Mg^{2+}$ efflux from perfused hearts. Furthermore, $Mg^{2+}$ efflux by phenylephrine was amplified by phorbol 12-myristate 13-acetate(PMA). This enhancement of $Mg^{2+}$ efflux by PMA was blocked by prazosin in perfused hearts. By contrast, the $Mg^{2+}$ influx could be induced by verapamil, nifedipine, ryanodine in perfused hearts, but not in myocytes. $W^7$, a $Ca^{2+}$/calmodulin antagonist, completely blocked the phenylephrine-induced $Mg^{2+}$ efflux in perfused hearts. In conclusion, $Mg^{2+}$ is responsible for the cardiac activity associated with ${\alpha}_1-adrenoceptor$ stimulation. The mobilization of $Mg^{2+}$ is decreased or increased by ${\alpha}_1-adrenoceptor$ stimulation in guinea pig hearts. These responses may be related specifically to the respective pathways of signal transduction. A decrease in $Mg^{2+}$ efflux by ${\alpha}_1-adrenoceptor$ stimulation in hearts can be through PKC dependent and intracellular $Ca^{2+}$ levels.

• 대한약리학회지
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• 제20권2호
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• pp.7-14
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• 1984

뇌척수제거 흰쥐에서 clonidine정맥주사에 의한 확장기 혈압상승작용(postsynaptic action)과 전기자극으로 야기된 빈맥의 심막충수 감소작용(presynaptic inhibitory action)에 대하여 ${\alpha}_1-$ 및 ${\alpha}_2-adrenoceptor$ 길항제의 영향을 관찰하였다. 삼환계 항우울약물인 imipramine을 단회 및 장기 투여하였을 때 clonidine에 의한 두 작용이 어떻게 영향을 받는가를 관찰하여 다음과 같이 요약하였다. 1) Clonidine의 혈압상승효과는 phentolamine이나 piperoxan 전처치에 의하여 길항되었으나, prazosin 전처치에 의하여는 길항되지 아니하였다. 2) Clonidine의 빈맥에 대한 억제작용은 prazosin에 의하여는 영향을 받지 아니하였으나, phentolamine 및 piperoxan 전처치에 의하여는 길항되었다. 3) Clonidine에 대한 혈압상승반응은 imipramine(20 mg/kg) 단회 및 장기 투여에 의하여 차단되었으며, 전자에서 보다 후자에서 더 현저하였다. 4) 빈맥에 대한 clonidine의 억제작용은imipramine단회 및 장기 투여에 의하여 모두 차단되었고, 양자간 에는 큰 차이가 없었다. 이상의 결과로 presynaptic ${\alpha}_2-adrenoceptor$는 imipramine 단회 투여에 의하여 억제되었고 장기 투여에 의하여는 pre- 및 postsynaptic ${\alpha}_2-adrenoceptor$ 둘 다 현저히 억제되었다. 이런 점으로 미루어 presynaptic ${\alpha}_2-adrenoceptor$의 감수성 저하가 삼환계 항우울제의 직접적인 작용기전일 것이라는 증거를 제시하기는 어렵다고 암시된다.

• 약학회지
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• 제30권3호
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• pp.157-162
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• 1986

$\alpha$-Adrenoceptor subtypes in the isolated rat aortic strips were examined by using agonists and antagonists which have varying selectivity for $\alpha_1$- and $\alpha_2$- adrenoceptors. Norepinephrine and phenylephrine produced a similar magnitude of maximum contractions. $pA_2$ values for prazosin and yohimbine were not significantly different using norepinephrine or phenylephrine as the agonist, suggesting a single population of alpha-adrenoceptor. Contractile responses produced by alpha-agonists were antagonized more effectively by prazosin (approximately 1000 fold) than by yohimbine.

• Biomolecules & Therapeutics
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• 제12권4호
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• pp.215-220
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• 2004

In an attempt to develop new anti-diabetic agents, a series of aryloxypropanolamine derivatives was synthesized to serve as ${\beta}_3$ adrenoceptor agonists. Among these derivatives, 1-{1-methyl-3-[4-(2-methyl-2H-1,2,3,4-tetrazol-5-yl)phenyl]propylamino}-3-phenoxy-2-propanol (KR60886) possessed a high affinity for the ${\beta}_3$ adrenoceptor (Ki = 28 nM) and moderate affinities for ${\beta}_1$ and ${\beta}_2$ adrenoceptors (Ki = 95 nM and 100 nM, respectively). In addition, KR60886 stimulated cAMP production with an EC$_{50}$ of 0.4 ${\mu}M$, confirming its agonistic activity for the ${\beta}_3$ adrenoceptor. In vivo activities of KR60886 were examined by using a fat-fed/streptozotocin (STZ)-treated rat model and the ob/ob mouse model. Oral administration of KR60886 (10 mg/kg) for 3 days (b.i.d.) to fat-fed/STZ-treated rats significantly lowered plasma glucose levels and reduced plasma free fatty acid concentrations. Similarly, KR60886 treatment (10 mg/kg/day for 7 d) resulted in a reduction of plasma glucose concentrations in ob/ob mice. The present study suggests that KR60886 is a potent ${\beta}_3$ receptor agonist with in vivo anti-diabetic properties.

• The Korean Journal of Physiology and Pharmacology
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• 제6권2호
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• pp.71-80
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• 2002

Previous studies have suggested that brain stem noradrenergic inputs differentially modulate neurons in the paraventricular nucleus (PVN). Here, we compared the effects of norepinephrine (NE) on spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) in identified PVN neurons using slice patch technique. In 17 of 18 type I neurons, NE $(30{\sim}100{\mu}M)$ reversibly decreased sIPSC frequency to $41{\pm}7%$ of the baseline value $(4.4{\pm}0.8\;Hz,\;p<0.001).$ This effect was blocked by yohimbine $(2{\sim}20{\mu}M),$ an ${\alpha}_2-adrenoceptor$ antagonist and mimicked by clonidine $(50{\mu}M),$ an ${\alpha}_2-adrenoceptor$ agonist. In contrast, NE increased sIPSC frequency to $248{\pm}32%$ of the control $(3.06{\pm}0.37\;Hz,\;p<0.001)$ in 31 of 54 type II neurons, but decreased the frequency to $41{\pm}7$ of the control $(5.5{\pm}1.3\;Hz)$ in the rest of type II neurons (p<0.001). In both types of PVN neurons, NE did not affect the mean amplitude and decay time constant of sIPSCs. In addition, membrane input resistance and amplitude of sIPSC of type I neurons were larger than those of type II neurons tested (1209 vs. 736 $M{\Omega},$ p<0.001; 110 vs. 81 pS, p<0.001). The results suggest that noradrenergic modulation of inhibitory synaptic transmission in the PVN decreases the neuronal excitability in most type I neurons via ${\alpha}_2-adrenoceptor,$ however, either increases in about 60% or decreases in 40% of type II neurons.

• 대한수의학회지
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• 제38권3호
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• pp.508-517
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• 1998

There is evidence that the sympathetic nervous system exerts a control on thyroid function via an adrenergic innervation of thyroid cells. Although it is clear that the inhibitory effects of catecholamines result from an activation of ${\alpha}_1$-adrenoceptors, the mechanisms involved in ${\alpha}_1$-stimulation are not fully understood. The effects of methoxamine and protein kinase C (PKC) activator on the release of thyroxine ($T_4$) from mouse thyroid were studied to clarify the role of PKC in the regulation of $T_4$ release in vitro. The glands were incubated in the medium, samples of the medium were assayed for $T_4$ by EIA kits. Methoxamine inhibited the TSH-stimulated $T_4$ release. This inhibition was reversed by prazosin, an ${\alpha}_1$-adrenergic antagonist. Futhermore, the inhibitory effect of methoxamine on the $T_4$ release stimulated by TSH was prevented by chloroethylclonidine, an ${\alpha}_{1b}$-adrenoceptor antagonist, but not by WB4101, an ${\alpha}_{1a}$-adrenoceptor antagonist. Also methoxamine inhibited the forskolin-, cAMP- or IBMX-stimulated $T_4$ release. These inhibition were reversed by PKC inhibitors, such as staurosporine and $H_7$. PMA, a PKC activator, completely inhibited the TSH-stimulated $T_4$ release, and its inhibition was reversed by staurosporine and $H_7$, but not by chelerythrine. R59022 (a diacylglycerol kinase inhibitor), like methoxamine, also inhibited the TSH-stimulated $T_4$ release, and its inhibition was also reversed by staurosporine. The present study suggests that methoxamine inhibition of $T_4$ release from mouse thyroid can be induced by activation of the ${\alpha}_{1b}$-adrenoceptors and that it is mediated through the ${\alpha}_1$-adrenoceptor-stimulated PKC formation.

• 대한한의학회지
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• 제25권3호
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• pp.67-77
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• 2004

Objectives : Many studies have reported that acupuncture analgesia was mediated through the activation of peripheral and central opioid receptors. However, there has been little electrophysiological study on the adrenergic mechanism of acupuncture analgesia in chronic inflammatory and neuropathic pain. The present study was undertaken to elucidate the role of adrenoceptors in the production of acupuncture analgesia in the chronic pain model. Methods : In the rat with chronic inflammation and nerve injury, dorsal horn cell (DHC) responses to afferent C fiber stimulation were used as a pain index and changes in electroacupuncture (EA) analgesia were recorded before and after intravenous administration of selective adrenoceptor antagonists. EA stimulations (2Hz, 0.5msec, 3mA) were applied to the contralateral Zusanli point for 30 min. Results : EA stimulation induced long-lasting inhibition of DHC responses in the rat with chronic inflammation and nerve injury. In both models of inflammation and neuropathic pain, α-adrenoceptor antagonist (phentolamine) significantly attenuated an inhibitory effect of EA on DHC responses. Selective α2-adrenoceptor antagonist (yohimbine) also had a similar suppressive action on DHC responses to that of phentolamine. However, β-adrenoceptor antagonist (propranolol) did not have any inhibitory effect on DHC responses in either model of chronic pain. Conclusions : These experimental findings suggest that in rats with chronic pain, EA stimulation with low frequency and high intensity produced an analgesic effect which was mediated through an activation of α2-adrenoceptors.