• The Korean Journal of Physiology and Pharmacology
• /
• 제5권5호
• /
• pp.423-431
• /
• 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
• /
• 제23권6호
• /
• pp.1090-1106
• /
• 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.

• 한국임상약학회지
• /
• 제21권1호
• /
• pp.6-13
• /
• 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.

• 대한약리학회지
• /
• 제31권3호
• /
• pp.333-344
• /
• 1995

fMLP에 의하여 자극된 중성호성 백혈구에서의 superoxide 생성, myeloperoxidase 유리, 칼슘 동원과 백혈구 부착에 나타내는 adenosine과 $N^6-cyclopentyladenosine$의 효과를 관찰하였다. 또한 이들의 효과를 C5a와 PMA의 자극효과에 대하여 그리고 lipopolysaccharide-primed 중성호성 백혈구의 반응에 대하여 관찰하였다. 이와 함께 adenosine의 억제작용에 있어 cAMP의 관여 여부를 조사하였다. 연구 결과로 부터 fMLP에 의해 자극된 중성호성 백혈구에서의 superoxide 생성, 탈과립과 세포내 칼슘 동원과 백혈구 부착은 adenosine 수용체에 의하여 조절된다고 추정된다. Adenosine은 protein kinase C의 활성화에 따른 백혈구 반응의 자극에 영향을 나타내지 않을 것으로 시사된다. Nonprimed 세포에 비하여, lipopolysaccharide-primed 중성호성 백혈구에서 fMLP에 의한 superoxide 생성은 adenosine의 영향을 적게 받을 것으로 여겨진다. Adenosine 존재하에서 백혈구 반응에 나타내는 theophylline의 억제효과는 세포내 cAMP 축적에 기인할 것으로 추정된다.

• BMB Reports
• /
• 제38권3호
• /
• pp.314-319
• /
• 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.

• 한국발생생물학회지:발생과생식
• /
• 제20권2호
• /
• pp.127-133
• /
• 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
• /
• 제22권3호
• /
• pp.225-234
• /
• 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
• /
• 제30권9호
• /
• pp.847-853
• /
• 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.

• 식물조직배양학회지
• /
• 제28권3호
• /
• pp.165-171
• /
• 2001

Adenosine deaminase 유전자를 연초의 형질전환용 표지유전자로 활용할 때 형질전환체 여부를 매우 빠르고 눈으로 직접 색깔을 확인할 수 있는 새로운 방법이 개발되었다. ADA 효소는 독성인 adenosine 유도체를 비독성인 inosine 유도체와 암모니아로 변환시키는데, 이때 형성된 암모니아를 phenol-nitoprusside와 alkaline-hypochlorite 용액을 이용하여 청색으로 변환시켜 96 well plate상에서 1시간 내에 형질전환체 여부를 쉽게 확인할 수 있게 되었다. ADA효소의 substrate로서 9-D-arabinofuranosyl adenine, cordycepin, 2'-deoxyadenosine, adenosine and xylofuranosyl adenine이 모두 가능하였으며, substrate 용액의 최적조건은 adenosine 10 mM과 pH 7.5이었다. 특히 형질전환체는 ADA효소의 inhibitor인 deoxycoformycin이 함유되어 있는 용액 속에서는 adenosine을 inosine과 암모니아로 변환시키지 못해 색깔의 변화가 없었는데, 이는 형질전환체에서 색깔의 변화는 ADA효소의 작용 때문에 일어나는 것을 의미한다. 따라서 본 연구결과는 ADA 표지유전자가 도입된 형질전환체의 확인에 있어서 GUS gene system과 같이 눈으로 직접 확인할 수 있을 뿐만 아니라 매우 작은 크기의 형질전환체 절편으로 쉽고, 빠르면, 값싸게 확인할 수 있게 되었다.

• The Korean Journal of Pain
• /
• 제24권1호
• /
• pp.7-12
• /
• 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.