• The Korean Journal of Physiology and Pharmacology
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• v.5 no.5
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• pp.423-431
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• 2001

Some recent investigations revealed that vasodilatory action of adenosine is mainly not mediated by surface A2 receptor and suggested the existence of an intracellular action site. In the present study, we tried to differentiate intracellular from extracellular site of adenosine action in the regulation of coronary flow. In perfused rabbit hearts, concentration-response curve of coronary flow to exogenous adenosine was constructed in the presence or absence of dipyridamole, an inhibitor of transmembrane purine transport. Inhibition of cellular adenosine uptake by dipyridamole suppressed the increase of flow rate while enhancing the decrease in heart rate induced by exogenous adenosine. In another series of experiments, perfused rabbit hearts were subjected to energy deprivation in order to increase the production of endogenous adenosine. Energy deprivation along with dipyridamole administration resulted in higher coronary flow rate. Lower perfusate adenosine concentration was observed along with higher tissue adenosine content in this group. These results implied that coronary flow rate is determined not by interstitial adenosine concentration but by intracellular activity of adenosine. To confirm the effects of dypiridamole in vivo, direct measurement of interstitial adenosine concentration by mycrodialysis along with the assay of intracellular adenosine content was performed after intranenous dipyridamole administration. After dipyridamole infusion, intracellular adenosine content was markedly increased while interstitial adenosine concentration was not altered. In another series of experiments, the right shift of concentration-response curve of adenosine-induced vasodilation by 8-phenyltheophilline, a representative adenosine receptor antagonist, was mostly abolished by prior administration of prazosin, indicating that the influence of 8-PT on the adenosine action is not attributed to the inhibition of A2 receptor but related to the suppression of ${\alpha}-adrenoceptor$ activation. From these results, we concluded that adenosine acts intracellularly to regulate the coronary blood flow.

• Journal of Chest Surgery
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• v.23 no.6
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• pp.1090-1106
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• 1990

This study was undertaken to investigate whether adenosine administered during cardioplegic arrest could enhance myocardial protection and improve recovery of function after ischemia. Isolated Langendorff-perfused rat hearts were subjected to 40 minutes of normothermic [37oC] ischemia. Control hearts [n=10] received modified St. Thomas’ cardioplegic solution, and the remaining hearts received modified St. Thomas’ cardioplegic solution with either 20 \ulcornerM [n=10], 200 \ulcornerM [n=10] adenosine. After ischemia of 40 minutes and 30 minutes of reperfusion, left ventricular contractility was superior in all groups of adenosine-treated hearts compared with control hearts. Furthermore, there was a significant incremental increase in functional recovery with increasing dose of adenosine. Post-ischemic diastolic stiffness was significantly better in all adenosine groups compared with controls. No differences were noted in coronary flow or myocardial water content between adenosine-treated and control hearts. These data demonstrate that adenosine administered in these concentrations provides myocardial protection, preservation of myocardial ATP and creatine phosphokinase and improved post-ischemic functional hemodynamic recovery after normothermic ischemia, presumably metabolically by reducing depletion of adenosine triphosphate, inducing rapid cardiac arrest and enabling improved post-ischemic recovery.

• Korean Journal of Clinical Pharmacy
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• v.21 no.1
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• pp.6-13
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• 2011

Bolus intravenous injection of adenosine resulted the temporal decrease of systemic blood pressure and heart rate in the anesthetized rats. Adenosine also resulted the persistent decrease of contractility and heart rate in the isolated spontaneously beating rat right atria. Both of the above inhibition effets of adenosine were increased by the pretreatment of NBI (nitrobenzylthioinosine), whitch is an adenosine transport inhibitor, but decreased by the pretreatment of 8- phenyltheophy1line, which is an adenosine antagonist. In isolated thoracic aorta ring segment of normotensive rats, intact rings were relaxed by adenosine ($42.3{\pm}8.7%$) and ATP ($85.9{\pm}15.8%$) in the concentration of $10^{-4}M$, but rubbed rings were relaxed by adenosine ($35.2{\pm}1.9%$) and ATP ($11.3{\pm}9.0%$) in $10^{-4}M$. After pretreatment of L-NAME (N-Nitro-Larginine methyl ester), which is an NO inhibitor, adenosine-induced relaxation was not affected, but ATP-induced relax ation was significantly inhibited (P<0.01). Meanwhile, adenosine resulted almost same as vasorelaxation in isolated thoracic aorta of SHR comparing to those of normotensive rats. But, vasodilation responses of ATP in intact rings of SHR are significantly inhibited comparing to those of normotensive rats. Adenosine-induced relaxation is attenuated after 8-phenyltheophylline pretreatment, but increased after NBI pretreatment. However, ATP-induced relaxations are not affected by 8-phenyltheophylline or NBI pretreatment. These results suggested that the hypotensive effects of adenosine was due to the decrease of contractile force and heart rate through the A1 receptor and vasodilation are mediated by A2 receptor of the vascular smooth muscle. And, the heart protective and vasodilation effects of adenosine might suggest that it would be useful in the acute treatment of coronary artery disease.

• The Korean Journal of Pharmacology
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• v.31 no.3
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• pp.333-344
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• 1995

The effects of adenosine and $N^6-cyclopentyladenosine$ (CPA) on superoxide production, myeloperoxidase release and $Ca^{2+}$ mobilization stimulated by fMLP in neutrophils were investigated. The effects were also observed on the stimulatory actions of C5a and PMA and the responses in lipopolysaccharide-primed neutrophils. In addition, the involvement of cAMP in the inhibitory action of adenosine was examined. The fMLP-stimulated neutrophil respiratory burst, degranulation and intracellular $Ca^{2+}$ mobilization may be regulated by activation of adenosine receptors. Adenosine may not affect the stimulated neutrophil responses due to activation of protein kinase C. fMLP-stimulated respiratory burst in lipopolysaccharide-primed neutrophils may be less sensitive to adenosine, compared with nonprimed cells. The inhibitory effect of theophylline in the presence of adenosine on neutrophil responses appears to be ascribed to accumulation of intracellular cAMP.

• BMB Reports
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• v.38 no.3
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• pp.314-319
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• 2005

Adenosine, as a ubiquitous metabolite, mediates many physiological functions via activation of plasma membrane receptors. Mechanisms of most of its physiological roles have been studied extensively, but research on adenosine-induced apoptosis (AIA) has only started recently. In this study we demonstrate that adenosine dose-dependently triggered apoptosis of cultured baby hamster kidney (BHK) cells. Adenosine-induced apoptotic cell death was characterized by DNA laddering, changes in nuclear chromatin morphology and phosphatidylserine staining. Apoptosis was also quantified by flow cytometry. Results suggest the involvement of adenosine $A_1$ and $A_3$ receptors as well as equilibrative nucleoside transporters in apoptosis induced by adenosine. These results indicate a receptor-transporter co-signaling mechanism in AIA in BHK cells. The involvement of $A_1$ and $A_3$ receptors also implies a possible apoptotic pathway mediated by G protein-coupled receptors.

• Development and Reproduction
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• v.20 no.2
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• pp.127-133
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• 2016

Purine metabolism is known factor for nuclear maturation of oocytes through both follicle cells and oocyte itself. However, it is largely unknown the roles of purine metabolism in the oocyte competence for fertilization and early development. In this study, the effects of adenosine in oocyte competence for development were examined using adenosine and its synthetic inhibitors. Adenosine treatment from GV intact stage for 18 hr (fGV) caused of decrease the fertilization rate but of increase the cleavage rate compared from the other stage treatment groups. Hadacidin did not effect on fertilization rate but increased cleavage rate without stage specificity. Adenosine did not block the effects of hadacidin with the exception of fGV group. Inhibition of purine synthetic pathways the fertilization rate was decreased in the fGV and fGVB groups but increased in the fMII group. Exogenous adenosine caused of decrease fertilization rate in the fGVB group but increase in the fMII group. Cleavage rate was dramatically increased in the adenosine treatment with synthetic inhibitors. It means that the metabolism of purine has stage specific effects on fertilization and cleavage. Exogenous adenosine had only can improve oocyte developmental competence when it treated at GV intact stage. On the other hand, endogenous synthesis in all maturation stage cause of increase the cleavage rate without effects on fertilization. These data suggest that adenosine at GV stage as a paracrine fashion and inhibitions of endogenous adenosine in all stage improve oocyte developmental competence.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.225-234
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• 2018

Adenosine is a naturally occurring breakdown product of adenosine triphosphate and plays an important role in different physiological and pathological conditions. Adenosine also serves as an important trigger in ischemic and remote preconditioning and its release may impart cardioprotection. Exogenous administration of adenosine in the form of adenosine preconditioning may also protect heart from ischemia-reperfusion injury. Endogenous release of adenosine during ischemic/remote preconditioning or exogenous adenosine during pharmacological preconditioning activates adenosine receptors to activate plethora of mechanisms, which either independently or in association with one another may confer cardioprotection during ischemia-reperfusion injury. These mechanisms include activation of $K_{ATP}$ channels, an increase in the levels of antioxidant enzymes, functional interaction with opioid receptors; increase in nitric oxide production; decrease in inflammation; activation of transient receptor potential vanilloid (TRPV) channels; activation of kinases such as protein kinase B (Akt), protein kinase C, tyrosine kinase, mitogen activated protein (MAP) kinases such as ERK 1/2, p38 MAP kinases and MAP kinase kinase (MEK 1) MMP. The present review discusses the role and mechanisms involved in adenosine preconditioning-induced cardioprotection.

• Journal of Chest Surgery
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• v.30 no.9
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• pp.847-853
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• 1997

Although the effects of adenosine on the heart, including the clinical suppression of cardiac arrhythmias, have been recognized for more than half a century, it is only in the last decade that the therapeutic potential of adenosine has been recognized. The objective of this study was to determine if augmentation of myocardial adenosine levels during global ischemia improves functional recovery after reperfusion. We used to modified Langendonf system to evaluate myocardial protective effect. Isolated rat hearts were subjected to 90 minutes of deep hypothermic arrest(15$^{\circ}C$) with modified St. Thomas'Hospital cardioplegic solution used to provide myocardial protection. Myocardial adenosine levels were augmented during ischemia by providing exogenous adenosine in the cardioplegic solution. Two groups of hearts w re studied: (1) control group(n=10) cardioplegia alone; (2) adenosine group(n=10) adenosine(0.75mg/kg/min) added to the cardioplegic solution. Significantly better percent recovery(p<0.01) in hemodynamics(except heart rate) at 60 minutes after reperfusion was evident compared to baseline values in the adenosine group. (systolic no란ic pressure : 78.5$\pm$3.6% vs 66.6$\pm$5.9%, airtic overflow volume : 61.7$\pm$ 11.6% vs 37.2$\pm$ 15.4%, coronary flow volume 77.1$\pm$7.5% vs 57.2$\pm$ 11.1%, and cardiac output : 65.6$\pm$ 11.5% vs 44.2$\pm$ 12.4%). Heart rate was similar in two groups(94.4$\pm$4.8% vs 95.3 $\pm$ 6.8%). Adenosine groups resulted in significantly rapid recovery time of heart beat after reperEusion(p<0.01) (24.5$\pm$7.6 sec. vs 179.0$\pm$ 131.1sec.). In biochemical study, CPK levels(0.1 $\pm$0.3U/L vs 1.4$\pm$0.8U/L) and lactic acid levels(0.08$\pm$0.Immol/L vs 0.34$\pm$0.2 mmol/L) were significantly low in adenosine groups(p<0.01). We concluded that adenosine included cardioplegia have better recovery effects after r perfusion in myocardial ischemia compared to adenosine free cardioplegia.

• Korean Journal of Plant Tissue Culture
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• v.28 no.3
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• pp.165-171
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• 2001

New visible and fast assay system have been developed for tobacco transformant introduced with adenosine deaminase (ADA) marker gene, which converts cytotoxic adenosine analogues to non-toxic inosine analogues and ammonia. Ammonia was changed to blue color in the solution of phenol-nitoprusside and alkaline-hypochlorite. It was possible to detect activity of ADA visibly on the holes of 96 well plate using tiny explant of transgenic tobacco leaves within 1 hour incubation time. As substrates of ADA enzyme from transgenic plant on the plate, a number of adenosine analogues such as 9-D-arabinofuranosyl adenine, cordycepin, 2'-deoxyadenosine, adenosine and xylofuranosyl adenine were possible for detection of ADA activity. Optimal condition of substrate for ADA enzyme was each 10 mM and pH 7.5 in adenosine solution. Especially, transgenic plant did not convert adenosine to inosine and ammonia in the presence of ADA inhibitor deoxycoformycin, which means that ammonia produced from transgenic plant is due to expression of ADA gene. Now, we show that this detection system can be easily, sensitively, fast and cheaply as well as visibly assayed in vitro as GUS gene system with very small size of transformant explant.

• The Korean Journal of Pain
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• v.24 no.1
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• pp.7-12
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• 2011

Background: Adenosine has been shown to have a wide spectrum of unique pain-relieving effects in various clinical situations. The aim of this study was to investigate the effects of intraoperative adenosine infusion on acute opioid tolerance and opioid induced hyperalgesia induced by remifentanil in adult patients undergoing tonsillectomy. Methods: For this study, ninety patients were randomly allocated into groups that receive either adenosine (adenosine group) or saline (remifentnail group) intravenously under remifentanil based anesthesia and saline (sevoflurane group) under sevoflurane anesthesia. The patients in adenosine group received adenosine at dose of $80\;{\mu}g$/kg/min, and those in remifentnail group and sevoflurane group received an equal volume of saline 10 minutes after the induction of anesthesia until the end of surgery. Intraoperative evaluation included time weighted mean remifentanil dose, and postoperative evaluations included degree of pain severity at 1, 6, 12, and 24 hours, time to first postoperative requirement, and analgesic dose required during 24 hours after operation. Results: Time weighted mean remifentanil dose during intraoperative period in adenosine group was significantly lower than that of remifentnail group (P = 0.00). The first postoperative analgesic were required earlier in remifentanil group than sevoflurane group or adenosine group (P = 0.00). Pethidine requirement during 24 hours in sevoflurane group and adenosine group was significantly lower than that of remifentnail group (P = 0.00). The visual analog scale scores for pain in sevoflurane group and adenosine group were significantly lower than those of remifentnail group for 12 hours after operation (P = 0.00). Incidence of hypotension (P = 0.024) and number of ephedrine administered (P = 0.011) in adenosine group were significantly higher than those of sevoflurane group. Conclusions: The above results suggest that intraoperative adenosine infusion prevent acute opioid tolerance and opioid induced hyperalgesia induced by remifentanil.