• Biomolecules & Therapeutics
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• 제25권3호
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• pp.329-336
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• 2017

Adipogenesis in murine preadipocyte 3T3L-1 has been used as a model system to study anti-obese bioactive molecules. During adipogenesis in 3T3-L1 preadipocytes, we found that capsanthin inhibited adipogenesis ($IC_{50}$; $2.5{\mu}M$) and also showed lipolytic activity in differentiated adipocytes from the preadipocytes ($ED_{50}$; 872 nM). We identified that the pharmacological activity of capsanthin on adipogenesis in 3T3-L1 was mainly due to its adrenoceptor-${\beta}_2$-agonistic activity. In high-fat diet animal model study, capsanthin significantly enhanced spontaneous locomotive activities together with progressive weight-loss. The capsanthin-induced activation of kinetic behavior in mice was associated with the excessive production of ATP initiated by both the enhanced lipolytic activity together with accelerated oxidation of fatty acids due to the adrenoceptor ${\beta}_2$-agonistic activity of capsanthin. Capsanthin also dose-dependently increased adiponectin and p-AMPK activity in high fat diet animals, suggesting that capsanthin has both anti-obesity and insulin sensitizing activities.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.29-29
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• 2003

Compartmentation of intracellular signaling pathways serves as an important mechanism conferring the specificity of G protein-coupled receptor (GPCR) signaling. In the heart, stimulation of $\beta$$_2$-adrenoceptor ($\beta$$_2$-AR), a prototypical GPCR, activates a tightly localized protein kinase A (PKA) signaling, which regulates substrates at cell surface membranes, bypassing cytosolic target proteins (eg, phospholamban). Although a concurrent activation of $\beta$$_2$-AR-coupled $G_{i}$ proteins has been implicated in the functional compartmentation of PKA signaling, the exact mechanism underlying the restriction of the $\beta$$_2$-AR-PKA pathway remains unclear. In the present study, we demonstrate that phosphatidylinositol 3-kinase (PI3K) plays an essential role in confining the $\beta$$_2$-AR-PKA signaling. Inhibition of PI3K with LY294002 or wortmannin enables $\beta$$_2$-AR-PKA signaling to reach intracellular substrates, as manifested by a robust increase in phosphorylation of phospholamban, and markedly enhances the receptor-mediated positive contractile and relaxant responses in cardiac myocytes. These potentiating effects of PI3K inhibitors are not accompanied by an increase in $\beta$$_2$-AR-induced cAMP formation. Blocking $G_{i}$ or $G_{$\square$$\square$}$ signaling with pertussis toxin or $\beta$ARK-ct, a peptide inhibitor of $G_{$\square$$\square$}$, completely prevents the potentiating effects induced by PI3K inhibition, indicating that the pathway responsible for the functional compartmentation of $\beta$$_2$-AR-PKA siglaling sequentially involves $G_{i}$, $G_{$\square$$\square$}$, and PI3K. Thus, PI3K constitutes a key downstream event of $\beta$$_2$-AR- $G_{i}$ signaling, which confines and negates the concurrent $\beta$$_2$-AR/Gs-mediated PKA signaling.gnaling.

• 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.

• 대한수의학회지
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• 제33권4호
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• pp.617-622
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• 1993

The preliminary studies on the localization of adrenoceptors were performed on smooth muscle strips of bovine esophageal groove. The mechanical activity of the muscle strip was recorded isometrically in vitro.w In the bottom circular muscle strips. the excitatory ${\alpha}-adrenergic$ responses were not blocked by tetrodotoxin$(2.1{\times}10^{-6}M)$ and denervation which was carried by cold storage of strips for 48 hrs in Tyrode's solution at $5-6{^{\circ}C}$ without oxygen supply. These excitatory ${\alpha}-adrenergic$ responses were partially blocked by atropine. In the lip longitudinal muscle strips, the inhibitory${\beta}-adrenergic$ responses were not blocked by pretreatment of tetrodotoxin and atropine. The results suggest that ${\beta}-adrenergic$ receptors mediating relaxations are located on the postsynaptic smooth muscle cells, whereas ${\beta}-adrenergic$ receptors mediating contractions are located both in the smooth muscle cells and in the cholinergic neurones.

• Biomolecules & Therapeutics
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• 제1권1호
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• pp.1-8
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• 1993

It has been known that calcium antagonists also inhibit the radioligand binding to muscarinic and $\alpha$-adrenergic receptors and, in case of verapamil, these inhibitions may play a role in the effects of verapamil on the heart. In this study, the effects of nicardipine, nifedipine, nimodipine, diltiazem and verapamil on the binding of [$^3H$]dihydroalprenolol (DHA) to dog cardiac ${\beta}$-adrenergic receptors were examined. A single uniform [$^3H$]DHA binding site ($K_D/= 5nM\;and\;B_{max}=2600$ fmol/mg protein) was identified in dog cardiac sarcolemma. [$^3H$]DHA binding was not affected by the usual therapeutic concentrations of these calcium antagonists (nanomolar range) but in the "nonspecific"concentration ranges ($28-180{\mu}m$) these drugs inhibited [$^3H$]DHA binding to $\beta$-adrenergic receptors. Nicardipine, nifedipine, nimodipine and diltiazem competed for [$^3H$]DHA binding to ${\beta}$-adrenergic receptors with dissociation constants ($K_i$) of $28{\mu}m,\' 74{\mu}m, 39{\mu}m \;and \;35{\mu}m,$ respectively. Verapamil ($K_i=176.5 {\mu}m$) was less potent inhibitor than other drugs and this inhibition was noncompetitive; the maximal binding capacity ($B_{max}$) $300 {\mu}m$ verapamil without change in the apparent dissociation constant (4K_D$) for DHA. These results indicate that the inhibitory action of calcium antagonists at high concentrations on ${\beta}$-adrenergic receptors is not involved in the therapeutic effects of these drugs by the calcium channel blocking action.

• Biomolecules & Therapeutics
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• 제25권1호
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• pp.4-11
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• 2017

Heterotrimeric G proteins are key intracellular coordinators that receive signals from cells through activation of cognate G protein-coupled receptors (GPCRs). The details of their atomic interactions and structural mechanisms have been described by many biochemical and biophysical studies. Specifically, a framework for understanding conformational changes in the receptor upon ligand binding and associated G protein activation was provided by description of the crystal structure of the ${\beta}2$-adrenoceptor-Gs complex in 2011. This review focused on recent findings in the conformational dynamics of G proteins and GPCRs during activation processes.

• 생물정신의학
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• 제2권2호
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• pp.205-217
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• 1995

1) Paroxetine이 5-HT흡수에 가장 강력하고, 선택적이었으며, 그 다음이 fluvoxamine, sertraline, fluoxetine순이었고, sertraline은 다른 SSRIs와는 달리 NE보다 DA억제작용이 더 강했다. 2) Paroxetine이 muscarinic cholinergic 수용체에 대한 친화력이 다소 높았을 뿐, 전반적으로 SSRIs는 histamine $H_1$과 ${\alpha}_1$에 대한 친화력은 약했다. 3) Paroxetine은 ${\beta}$-adrenoceptor와 cyclic AMP에 영향을 미치지 않는 반면, sertraline은 ${\beta}$-adrenoceptor와 cyclic AMP의 감소를 가져왔다. 4) SSRIs의 생체이용율은 대략 50%이었으며, 투약후 2~8시간 사이에 최고혈중농도에 도달하였으며, 특히 sertraline은 음식물과 같이 복용시 혈장의 concentration time curve와 최고 농도를 증가시켰다. 5) Sertraline은 혈중농도가 용량에 비례하였으며, 모든 SSRIs는 비교적 큰 용량분포를 보이고, 높은 비율로 혈장 단백질과 결합되어 있었다. 6) Fluoxetine 대사물의 5-HT 억제 작용이 제일 강했다. 그러나 paroxetine, fluoxetine, sertraline 대사물은 강도는 서로 다르지만 간의 isoenzyme IID6를 억제하며, 그 중에서 paroxetine의 억제작용이 제일 강력하다. 7) Sertraline은 TCAs나 haloperidol과 병합사용시 TCAs나 haloperidol의 혈중농도의 유의한 변화가 없었으며, MAOI A형인 moclobemide와 비교적 안전하게 병용 치료할 수 있다. 8) SSRIs는 TCAs와 비교해볼 때 치료효과는 유사하였으나 fluvoxamine은 자살사고에, paroxetine은 우울중에서 나타나는 불안과 운동성 초조증에 효과적이다. 9) 급성 우울증 삽화시 현저한 효과를 보인 후 적어도 4개월 이상의 유지치료기간이 필요하다. 10) SSRIs는 위장관계통의 부작용이 가장 많았고, 부작용은 일반적으로 분복한 경우가 적었다.

• Tuberculosis and Respiratory Diseases
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• 제46권6호
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• pp.826-835
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• 1999

연구배경 : $\beta_2$ 교감신경 수용체의 다형성이 기관지 천식의 표현형에 영향을 미친다고 알려져 있다. 이에 저자들은 먼저 기관지 천식 환자와 정상인에서의 $\beta_2$ 교감신경 수용체의 다형성의 빈도에 차이가 있는가를 알아보고, 또한 기관지 천식 환자에서 아토피의 유무 및 혈청 총 IgE의 증가 여부와 $\beta_2$ 교감신경 수용체의 다형성이 관계가 있는지 알아보고자 본 연구를 시행하였다. 방 법 : 기관지 천식 환자 109명과 정상인 42명에 대하여 혈청 총 IgE를 측정하고, 항원 특이 IgE 검사 및 피부 단자 검사를 실시하였고, mutated allele specific amplification 법으로 $\beta_2$ 교감신경 수용체와 다형성을 검색하였다. 결 과 : $\beta_2$ 교감신경 수용체의 다형성을 조사한 결과 16번 아미노산 위치에서는 Arg 야생형 및 Arg/Gly 이형접합체 변이형, Gly 동형 접합체 변이형이, 그리고 27번은 Gln 야생형, Gln/Glu 이형 접합체 변이형, Glu 동형 접합체 변이형이 관찰되었다. 34번 아미노산의 경우는 Val 야생형과 Val/Met 이형 접합체 변이형이, 164번은 Thr 야생형만 있었다. 1) 정상인과 기관지 천식 환자에서 $\beta_2$ 교감신경 수용체의 16, 27, 34번 아미노산 위치에 있어서 다형성의 빈도는 통계학적으로 차이가 없었다(p>0.05)(Table 3). 2) 기관지 천식환자에서 $\beta_2$ 교감신경 수용체 다형성의 빈도와 아토피의 존재 유무는 16, 27, 34 번 아미노산에서 모두 통계학적으로 관계가 없었다(p>0.05) (Table 4). 3) 기관지 천식 환자 중 혈청 총 IgE가 증가된 군과 정상 군에서 $\beta_2$ 교감신경 신경 수용체 다형성과 혈청 총 IgE의 증가 여부의 비교는 16, 27, 34번 아미노산 모두 통계학적인 관련이 없었다(p>0.05) (Table 5). 결 론 : 결론적으로 기관지 천식 환자와 정상인 사이의 $\beta_2$ 교감신경 수용체의 다형성은 16, 27, 34번 아미노산 위치에서 차이가 없었고, 기관지 천식환자에서 아토피의 유무 및 혈청 총 IgE의 증가 여부와 $\beta_2$ 교감신경 수용체의 다형성의 빈도는 통계적으로 유의한 관계가 없었다.

• 대한약리학회지
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• 제28권1호
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• pp.19-25
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• 1992

Nonbenzodiazepine계 항불안제인 buspirone을 이용하여 건강한 8명의 남자를 대상으로 prolactin과 cortisol분비를 측정하였다. Buspirone는 $Dopamine_2$ 수용체 antagonist 성질 뿐 아니라 $5-HT_{1A}$ partial agonist 효과가 있는 것으로 보고되고 있다. Buspirone 30mg 경구투여시 혈청 prolactin 농도는 유의한 증가를 보였으나 혈청 cortisol 농도의 변화는 차이가 없었다. beta adrenoreceptor antagonist이면서 $5-HT_{1A}$ 수용체 antagonist로 알려진 pindolol (30mg)을 경구 투여한 결과 기초 혈청 prolactin이나 cortisol 농도는 유의한 차이가 없었다. Pinodlol을 전처치한 경우 buspirone-induced prolaction 분비의 유의한 억제효과는 없었다. 이상의 성적은 buspirone-induced prolactin 분비증가는 아마도 $5-HT_{1A}$ 수용체 활성과 관련되지 않음을 시사하는 것으로 사료된다.

• The Korean Journal of Physiology
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• 제25권2호
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• pp.147-158
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• 1991

The effects of noradrenaline on the spontaneous contraction recorded from a strip of mucosa-free antral circular muscle were studied in the guinea-pig stomach, and the changes in slow waves and membrane resistance were analyzed in order to elucidate the mechanism for the excitatory response to noradrenaline. Electrical responses of circular muscle cells were recorded using glass microelectrodes filled with 3 M KCI. Electrotonic potentials were produced to estimate membrane resistance by the partition stimulating method. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C$. The results obtained were as follows: 1) The spontaneous contractions were potentiated dose-dependently by the application of noradrenaline. 2) Through the experiments using adrenoceptor-blockers, the strong excitatory effect via $[\alpha}-adrenoceptors$ and the weak inhibitory efffect via ${\beta}-adrenoceptors$ were noted. 3) Noradrenaline produced hyperpolarization of membrane potential, and increases in the amplitude and the maximum rate of rise of slow waves. 4) In the presence of apamin, Ca-dependent K channel blocker, the characteristic hyperpolarization was not developed. However, the excitatory effect of noradrenaline on spontaneous contraction remained. 5) Membrane resistance was reduced during the hyperpolarized state by the application of noradrenaline, and the change of membrane resistance and the hyperpolarized state were completely abolished by apamin. From the above results, following conclusions could be made: Excitatory responses to noradrenaline result from the dominant ${\alpha}-excitatory$, and the weak ${\beta}-inhibitory$ action of noradrenaline. Hyperpolarization of membrane potential by noradrenaline is due to the activation of Ca-dependent K channel.