• The Korean Journal of Physiology and Pharmacology
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• 제11권2호
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• pp.37-43
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• 2007

Adenosine has been reported to provide cytoprotection in the central nervous systems as well as myocardium by activating cell surface adenosine receptors. However, the exact target and mechanism of its action still remain controversial. The present study was performed to examine whether adenosine has a protective effect against $A{\beta}$-induced injury in neuroglial cells. The astrocyte-derived human neuroglioma cell line, A172 cells, and $A{\beta}_{25{\sim}35}$ were employed to produce an experimental $A{\beta}$-induced glial cell injury model. Adenosine significantly prevented $A{\beta}$-induced apoptotic cell death. Studies using various nucleotide receptor agonists and antagonists suggested that the protection was mediated by $A_1$ receptors. Adenosine attenuated $A{\beta}$-induced impairment in mitochondrial functional integrity as estimated by cellular ATP level and MTT reduction ability. In addition, adenosine prevented $A{\beta}$-induced mitochondrial permeability transition, release of cytochrome c into cytosol and subsequent activation of caspase-9. The protective effect of adenosine disappeared when cells were pretreated with 5-hydroxydecanoate, a selective blocker of the mitochondrial ATP-sensitive $K^+$ channel. In conclusion, therefore we suggest that adenosine exerts protective effect against $A{\beta}$-induced cell death of A172 cells, and that the underlying mechanism of the protection may be attributed to preservation of mitochonarial functional integrity through opening of the mitochondrial ATP-sensitive $K^+$ channels.

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.753-761
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• 1998

Preconditioning of a heart with small doses of catecholamines induces a tolerance against the subsequent lethal ischemia. The present study was performed to find a specific receptor pathway involved with the catecholamine preconditioning and to test if adenosine plays a role in this cardioprotective effect. Isolated rat hearts, pretreated with small doses of ${\alpha}-\;or\;{\beta}-adrenergic$ agonists/antagonists, were subjected to 20 minutes ischemia and 20 minutes reperfusion by Langendorff perfusion method. Cardiac mechanical functions, lactate dehydrogenase and adenosine release from the hearts were measured before and after the drug treatments and ischemia. In another series of experiments, adenosine $A_1\;or\;A_2$ receptor blockers were treated prior to administration of adrenergic agonists. Pretreatments of a ${\beta}-agonist,\;isoproterenol(10^{-9}{\sim}10^{-7}\;M)$ markedly improved the post-ischemic mechanical function and reduced the lactate dehydrogenase release. Similar cardioprotective effect was observed with an ?-agonist, phenylephrine pretreatment, but much higher $concentration(10^{-4}\;M)$ was needed to achieve the same degree of cardioprotection. The cardioprotective effects of isoproterenol and phenylephrine pretreatments were blocked by a ${\beta}_1-adrenergic$ receptor antagonist, atenolol, but not by an ${\alpha}_1-antagonist,$ prazosin. Adenosine release from the heart was increased by isoproterenol, and the increase was also blocked by atenolol, but not by prazosin. A selective $A_1-adenosine$ receptor antagonist, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) blocked the cardioprotection by isoproterenol pretreatment. These results suggest that catecholamine pretreatment protects rat myocardium against ischemia and reperfusion injury by mediation of ${\beta}_1-adrenergic$ receptor pathway, and that adenosine is involved in this cardioprotective effect.

• Archives of Pharmacal Research
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• 제15권1호
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• pp.73-77
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• 1992

From the roots of Angelica dahurica Bentham et Hooker (Umbelliferae), five coumarin glucosides together with adenosine have been isolated and identified as nodakenin, 3'-hydroxymarmesinin, tert-O-$\beta$-D-glucopyranosyl-byakangelicin, sec-O-$\beta$-D-glucopyranosyl-byakangelicin and scopolin. This is the first report of the occurrence of these compounds in this plant.

• IMMUNE NETWORK
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• 제9권6호
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• pp.255-264
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• 2009

Background: Chronic low grade inflammation is closely linked to type II diabetes, obesity, and atherosclerosis. Macrophages play a key role in the regulation of pro- or anti-inflammatory actions at the lesion sites of disease. Components of cordyceps militaris, cordycepin and adenosine, have been used for the modulation of inflammatory diseases. The effects of cordycepin in the modulation of macrophages have yet to be be elucidated. We investigated the effects of cordycepin and adenosine on the morphological changes of macrophages under the inflammatory condition of LPS and an anti-inflammatory condition involving high concentrations of adenosine. Methods: We confirmed the mRNA levels of the M1/M2 cytokine genes through RT-PCR and morphological change. Results: LPS-activated macrophages returned to their inactivated original shape, i.e., they looked like naive macrophages, through the treatment with high concentrations of cordycepin ($40{\mu}g/ml$). LPS and adenosine activated macrophages also returned to their original inactivated shapes after cordycepin treatment; however, at relatively higher levels of cordycepin than adenosine. This change did not occur with relatively low concentrations of cordycepin. Adenosine down-regulated the gene expression of M1 cytokines (IL-$1{\beta}$, TNF-${\alpha}$) and chemokines (CX3CR1, RANTES), such as cordycepin. Additionally, M2 cytokines (IL-10, IL-1ra, TGF-${\beta}$) were up-regulated by both cordycepin and adenosine. Conclusion: Based on these observations, both cordycepin and adenosine regulated the phenotypic switch on macrophages and suggested that cordycepin and adenosine may potentially be used as immunomodulatory agents in the treatment of inflammatory disease.

• Bulletin of the Korean Chemical Society
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• 제31권2호
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• pp.442-446
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• 2010

Adenosine 3',5'-cyclic monophosphate (cAMP) is a second messenger responsible for a multitude of cellular responses. In this study, we utilized $\beta$-cyclodextrin ($\beta$-CD) as an artificial receptor with a hydrophobic cavity to elucidate the inclusion kinetics of cAMP in a hydrophobic environment using the ultrasonic relaxation method. The results revealed that the interaction of cAMP with $\beta$-CD followed a single relaxation curve as a result of host-guest interactions. The inclusion of cAMP into the $\beta$-CD cavity was found to be a diffusion-controlled reaction. The dissociation of cAMP from the $\beta$-CD cavity was slower than that of adenosine 5'-monophosphate (AMP). The syn and anti glycosyl conformations of adenine nucleotides are considered to play an important role in formation of the inclusion complex. Taken together, our findings indicate that hydrophobic interactions are involved in the inclusion complex formation of cAMP with $\beta$-CD and provide insight into the interactions of cAMP with cAMP-binding proteins.

• 대한화학회지
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• 제45권4호
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• pp.312-317
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• 2001

7'-Aldehyde-nucleoside 유사체(2a, 2c)을 6-N-benzoyl-2',3'-O-isopropylideneadenosiner과 uridine으로부터 합성하였다. 2와 Wittig reagent인 ethoxycarbonylmethylene을 축합시켜 ethoxycarbonyl group을 갖는 탄소수를 증가시킨 공액 이중 결합을 지닌 nucleosi de 유사체, ethyl-1',5',6',7',8'-pentadeoxy-1'-(adenin-9-yl)-$\beta$-D-ribo-nnona-5'(E).7'(E)-dienofuranuronate(4b), ethyl-1',5',6',7',8'-pentadeoxy-1'-(uracyl-1-yl)-$\beta$-D-ribo-nona-5'(E),7'(E)-dienofuranuronate(4c)을 얻었다. 또한 2와 CBr4, Ph3P을 반응시켜 공액 이중 결합을 지닌 9-[8',8'-dibromo-5',6',7',8'-tetradeoxy-$\beta$-D-ribo-octa-5'(E),7'(E)-diene]nucleosides (6b,6c) 유사체를 각각 합성하였다.

• 임산에너지
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• 제21권1호
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• pp.16-24
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• 2002

저령의 균획으로부터 3개의 알카로이드와 2개의 스테로이드 화합물을 분리하였다. 단리된 물질들은 NMR, MS 등의 기기분석에 의해 9-β-D-ribofuranosyladenine (adenosine)을 비롯하여 1-β-D-ribofuranosyluracil (uridine), 그리고 2, 4-pyrimidinedione (uracil)과 ergosta-4, 6, 8 (14), 22-tetraen-3-one, ergosta-5, 7, 22-tritene-3β-ol (ergosterol)으로 각각 동정하였다.

• 식물조직배양학회지
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• 제22권4호
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• pp.235-240
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• 1995

식물세포의 형질전환을 위한 새로운 표지유전자의 개발은 식물유전공학의 중요한 관건이 되고 있다. 본 실험은 독성 adenosine 유도체인 9-$\beta$-D-arabinofuranosyl adenine (Ara-A)과 cordycepin등에 저항을 나타내는 adenosine deaminase (ADA) 유전자를 새로운 식물세포의 형질전환용 표지유전자로 사용코자 수행하였다. 정상식물체에서는 치사하는 농도인 Ara-A 100 $\mu$M과 cordycepin 50 $\mu$M이 함유된 선발배지에서 ADA 유전자에 의하여 형질전환된 연초식물체는 생존이 가능하였으며 성공적으로 형질전환체를 선발할 수 있었다. 또한 형질전환된 연초식물체에서 획득한 종자도 동일한 선발배지에서 ADA 유전자가 유전된 종자와 유전되지 않은 종자를 쉽게 구별할 수 있었다. 이런 결과는 동물유전자인ADA 유전자를 연초조직의 새로운 형질전환용 표지유전자로 사용할 수 있음을 시사한다.

• 대한약리학회지
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• 제32권1호
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• pp.1-11
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• 1996

흰쥐 해마(hippocampus)에서 norepinephrine(NE) 유리에 미치는 $A_1-adenosine$ 수용체의 post-receptor 기전에 관한 지견을 얻고자 하여 $^3H-norepinephrine$으로 평형시킨 해마 절편을 사용하여 adenosine의 $^3H-NE$ 유리에 미치는 여러가지 약물의 영향을 관찰하였다. Adenosine($1{\sim}30{\mu}M$)은 전기자극(3 Hz, 2 ms, 5 Vcm-1, 구형파)에 의한 NE 유리를 용량 의존적으로 감소시켰고, 이 효과는 선택적인 $A_1-adenosine$ 수용체 차단제인 $8-cyclopentyl-1,3-dipropylxanthine(2{\mu}M)$에 의해 차단되었다. G-단백 억제제인 N-ethylmaleimide(NEM, 10과 $30{\mu}M$)는 그 자체로써 전기자극으로 유발시킨 NE 유리를 증가시켰으며, adenosine의 NE 유리 억제효과는 NEM 전처리에 의하여 완전히 소실되었다. Protein kinase C 활성화제인 $4{\beta}-phorbol$ 12,13-dibutyrate(PDB, $1{\mu}M$)는 NE 유리 증가를 일으켰고, 이 효소 억제제인 $4{\beta}-polymyxin$ B(PMB, 0.1 mg)는 NE 유리감소를 일으켰으며, adenosine에 의한 NE 유리 감소효과는 PDB에 의해 억제되었고, PMB 전처리하에서는 감소효과가 출현하지 않았다. $Ca^{2+}$-통로 차단제인 $nifedipine(1{\mu}M$)은 adenosine의 NE 유리 억제효과에 영향을 미치지 못하고, ATP에 의존적인 $K^+-$통로 차단제인 glibenclamide역시 adenosine의 NE 유리 억제효과에 영향을 미치지 못하였다. 그러나 delayed rectifier $K^+-$통로 차단제인 tetraethylammonium(TEA, 3 mM)은 그 자체로 NE 유리를 증가 시켰으며, adenosine의 NE 유리 억제효과를 차단함을 볼 수 있었다. 8-bromo-cAMP(100과 $300{\mu}M$) 그 자체로는 NE 유리에 별다른 영향을 미치지 못하였으나 8-bromo-cAMP 전처리에 의하여 adenosine의 NE 유리 억제효과가 억제됨을 볼 수 있었다. 이상의 실험결과로 흰쥐 해마에서 $A_1-adenosine$ 수용체를 통한 adenosine의 NE 유리 감소는 G-단백에 의존적이며, 이러한 효과에 protein kinase C, TEA에 예민한 $K^+-$통로 및 adenylate cyclase계가 복합적으로 관여하고 nifedipine에 예민한 $Ca^{2+}-$통로와 glibenclamide에 예민한 $K^+-$통로는 관여하지 않는 것으로 사료된다.

• 생약학회지
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• 제27권1호
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• pp.15-19
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• 1996

In the course of phytochemical studies of Chrysanthermi Flos(Chrysanthemum indicum L., Compositae), two compounds were isolated by repeated column chromatography. Compound 1 is identified as adenosine on the basis of spectroscopic means and comparison with an authentic standard. Compound 2 is determined to be a new alkyl alcohol glycoside, 1-octen-3-ol $3-O-{\beta}-D-xylopyranosyl(1{\rightarrow} 6)-{\beta}-D-glucopyranoside$ on the spectroscopic evidence. Compounds 1 and 2 are reported for the first time from this plant.