• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.23-29
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• 1996

According to the traditional receptor model, competitive antagonists share with agonists the ability to bind to a common site on receptors, but they are different from agonist in that they cannot trigger the biological response-i.e., they lack intrinsic efficacy. Recent findings extend the model by indicating that not all antagonists display an intrinsic efficacy of zero but that some display 'inverse agonism'. In the present study we studied the inverse agonism at $A_1$ adenosine receptors in membranes prepared from rat cerebral cortex. Eight commercially available $A_1$ adenosine receptor antagonists (CGS-15943, ADPX, CPT, DPCPX, DPX, N-0840, PACPX and 8-PT) were screened for inverse agonism by measuring the extent of $[^{35}S]guanosine-5'-({\gamma}-thio)$ triphosphate $([^{35}S]GTP_{\gamma}S)$ binding to G proteins. The agonist-induced stimulation of $[^{35}S]GTP_{\gamma}S$ bindings was completely blocked in the presence of $A_1$ adenosine receptor antagonists. Under optimal conditions, two types of antagonists could be distinguished. Seven antagonists including DPCPX decreased the basal $[^{35}S]GTP_{\gamma}S$ binding in the absence of agonist, displaying inverse agonist activity. One (CGS-15943) had no effect on the basal bindings. N-ethylmaleimide treatment reduced the basal bindings as well as agonist-mediated stimulation of $[^{35}S]GTP_{\gamma}S$ bindings, indicating that a substantial amount of this binding reflects an activated state of the C proteins. In good agreement with these findings, 0.1 mM GTP decreased the apparent affinity of the receptors for the agonist PIA, increased that for DPCPX, and had no effect on that for CGS-15943.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.21-29
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• 2004

Purpose: Much evidence suggests long-term cigarette smoking alters coronary vascular endothelial response. On this study, we applied nonnegative matrix factorization (NMF), an unsupervised learning algorithm, to CO-less $H_2^{15}O-PET$ to investigate coronary endothelial dysfunction caused by smoking noninvasively. Materials and methods: This study enrolled eighteen young male volunteers consisting of 9 smokers $(23.8{\pm}1.1\;yr;\;6.5{\pm}2.5$ pack-years) and 9 nonsmokers $(23.8{\pm}2.9 yr)$. They do not have any cardiovascular risk factor or disease history. Myocardial $H_2^{15}O-PET$ was performed at rest, during cold ($5^{\circ}C$) pressor stimulation and during adenosine infusion. Left ventricular blood pool and myocardium were segmented on dynamic PET data by NMF method. Myocardial blood flow (MBF) was calculated from input and tissue functions by a single compartmental model with correction of partial volume and spillover effects. Results: There were no significant difference in resting MBF between the two groups (Smokers: 1.43 0.41 ml/g/min and non-smokers: $1.37{\pm}0.41$ ml/g/min p=NS). during cold pressor stimulation, MBF in smokers was significantly lower than 4hat in non-smokers ($1.25{\pm}0.34$ ml/g/min vs $1.59{\pm}0.29$ ml/gmin; p=0.019). The difference in the ratio of cold pressor MBF to resting MBF between the two groups was also significant (p=0.024; $90{\pm}24%$ in smokers and $122{\pm}28%$ in non-smokers.). During adenosine infusion, however, hyperemic MBF did not differ significantly between smokers and non-smokers ($5.81{\pm}1.99$ ml/g/min vs $5.11{\pm}1.31$ ml/g/min ; p=NS). Conclusion: in smokers, MBF during cold pressor stimulation was significantly lower compared wi4h nonsmokers, reflecting smoking-Induced endothelial dysfunction. However, there was no significant difference in MBF during adenosine-induced hyperemia between the two groups.

• Korean Journal of Agricultural Science
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• v.41 no.4
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• pp.433-440
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• 2014

This study was conducted to investigate the effect of age on the contents of carnitine, free amino acid, and nucleotide-related compound in Holstein calf meat. Twenty calves were allocated into four age groups (3, 6, 9, or 12 mon of age; n=5/group), and ribeye (M. longissimus dorsi) and top round (M. semimembranosus) were excised from left side of each carcass on day 1 post-mortem. Carnitine contents for ribeye and top round were 0.79~1.16 and 0.65~1.26 mg/100 g, respectively, and those showed a tendency to be the highest in 3 mon group. The contents of majority of free amino acids were the highest (p<0.05) in ribeye and top round from 12 mon group. The contents of adenosine monophosphate, inosine monophosphate, and inosine were the highest (p<0.05) in ribeye and top round from 12 mon group, but hypoxanthine content was the lowest (p<0.05) in those from 12 mon group. These findings suggest that age decreases the carnitine content but increases free amino acid and good taste-related nucleotides contents in Holstein calf meat.

• The Korean Journal of Physiology
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• v.21 no.2
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• pp.225-239
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• 1987

The effects of adenosine on the mechanical contractions and electrical activities were investigated in guinea-pig stomach. Spontaneous contractions of the antral region were recorded with force transducer, and the phasic contractions of fundic region were induced by electrical field stimulation. Electrical responses of smocth muscle cells were recored using glass capillary microelectrodes filled with 3M-KCl. Field stimulation was applied transmurally by using a pair of platinum wire (0.5 mm in diameter) placed on both sides of tissue. 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) Adenosine suppressed the spontaneous contractions of antrum in a dose-dependent manner. 2) The inhibitory effect on antral spontaneous contractions was not influenced by the administration of guanethidine $(5{\times}10^{-6}\;M)$ and atropine $10^{-6}\;M$, or in the presence of dipyridamole $10^{-7}\;M$. 3) The phasic contractions of fundus induced by electrical field stimulation, which disappeared rapidly by the addition of tetrodotoxin $(3{\times}10^{-7}\;M)$, were potentiated by adenosine in the presence of guanethidine. 4) Adenosine decreased the amplitude and the maximum rate of rise of slow waves, and the increased amplitude and rate of rise evoked in the high calcium solution or in the presence of TEA were decreased by adenosine. 5) The non-adrenergic, non-cholinergic inhibitory junction potential (IJP) was inhibited by adenosine in the antral region, while the excitatory junction potential (EJP) in the fundic region was potentiated. From the above results, the following conclusions could be made. 1) Adenosine suppresses the spontaneous contractions of antrum strip by the decrease in amplitude and rate of rise of slow waves. 2) The release of neurotransmitter(s) from non-adrenergic, non-cholinergic nerve terminals is inhibited by adenosine.

• Journal of Chest Surgery
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• v.43 no.1
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• pp.25-32
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• 2010

Background: Patients with vascular diseases commonly have coronary artery disease and associated cardiac problems. Therefore, their underlying heart diseases may be induced or exacerbated after vascular surgery. The effectiveness of SPECT imaging, which is a relatively simple and non-invasive imaging modality, for assessing these underlying heart diseases is still controversial. This study was performed to evaluate the clinical effect of tests and treatment based on SPECT imaging prior to vascular surgery on the development of post-operation cardiac complications. Material and Method: Sixty three patients who were treated at Inje University Pusan Paik Hospital between April 2004 and September 2007 and who underwent adenosine infusion technetium-99m (Tc-99m) tetrofosmin SPECT imaging prior to vascular surgery were selected for this study and we retrospectively reviewed their records. Result: The sensitivity and specificity of detecting a perfusion defect on SPECT to predict the development of cardiac complications was relatively low at 41.2% and 52.2%, respectively. However when coronary angiographies were done on the patients with abnormal SPECT and this was followed by aggressive treatment such as coronary artery intervention and coronary artery bypass grafting based on the angiography results, there was a tendency for lower cardiac complication rates. Conclusion: SPECT imaging shows low effectiveness as a screening test for predicting cardiac complications after vascular surgery.

• Journal of Chest Surgery
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• v.16 no.2
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• pp.199-212
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• 1983

The inhibition/influences of adenine compounds on the heart have been described repeatedly by many investigators, since the first report by Druny and Szent-Gyorgyi [1929]. These studies have shown that adenosine and adenine nucleotides have an over-all effect similar to that of acetylcholine [ACh] by slowing and weakening the heartbeat. The basic cellular and membrane events underlying the inhibitory action of adenosine on sinus rate, however, are not well understood. Furthermore, the physiological role of adenosine in regulation of the heartbeat remains still to be elucidated. Therefore, this study was undertaken in order to examine the response of rabbit SA node to adenosine and to compare the response to that of ACh. Isolated SA node preparation, whole atrial pair, or left atrlal strip was used in each experiment. Action potentials of SA node were recorded through the intracellular glass microelectrodes, which were filled with 3M KCI and had resistance of 30-50 M. All experiments were performed in a bicarbonate-buffered Tyrode solution which was aerated with 3% $CO_2-97%$ $O_2$ gas mixture and kept at $35^{\circ}C$. Spontaneous firing rate of SA node at 35C [Mean + SEM, n=16] was 154 + 3.3 beats/min. The parameters of action potentials were: maximum astolic potential [MDP], -731.7mV: overshoot [OS], 9 + 1.4mV; slope of pacemaker potential [SPP], 94 3.0mV/sec.Adenosine suppressed the firing rate of SA node in a dose dependent manner. This inhibitory effect appeared at the concentration of $10^{-6}M$ and was potentiated in parallel with the increase in adenosine concentration. Changes in action potential by adenosine were dose-dependent increase of MDP and decrease of SPP until $10^{-4}$. Above this concentration, however, the amplitude of action potential decreased markedly due to the simultaneous decrease of both MDP and OS. All these effects of adenosine were not affected by pretreatment of atropine [2mg/l] and propranolol [$5{\times}10^{-6}M$]. ACh [$10^{-6}M$] responses on action potential were similar to those of adenosine by increasing MDP and decreasing SPP. These effects of ACh disappeared by pretreatment of atropine [2mg/1]. Inhibition/effects of adenosine and ACh on sinus rate were enhanced synergistically with the simultaneous administration of adenosine and ACh. Marked decrease of overshoot potential was the most prominent feature on action potential. Dipyridamole [DPM], which is known to block the adenosine transport across cell membrane, definitely potentiated the action of adenosine . Adenosine suppressed the sinus rate and atrial contractility in the same dosage range, even in the reserpinized preparation. Above` results suggest that adenosine suppresses pacemaker activity, like ACh, by acting directly on the membrane of SA node, increasing MDP and decreasing SPP.

• Journal of Life Science
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• v.25 no.5
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• pp.607-614
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• 2015

Cancers are the largest cause of mortality and morbidity all over the world. Cordycepin, an adenosine analog, is a major functional component of the Cordyceps species, which has been widely used in traditional Oriental medicine. Over the last decade, this compound has been reported to possess many pharmacological properties, such as an ability to enhance immune function, as well as anti-inflammatory, antioxidant and anti-cancer effects. Recently, numerous studies have reported interesting properties of cordycepin as a chemopreventive agent as well. There is an accumulating body of experimental evidences suggesting that cordycepin impedes cancer progression by promoting apoptosis, inducing cell cycle arrest, modulating intracellular signaling pathways, and inhibiting invasion and metastasis of cancer cells. In many cancer cell lines, cordycepin inhibits growth and cell cycle progression by inducing arrest of the G2/M phase, resulting from the inhibition of retinoblastoma protein phosphorylation and induction of cyclin-dependent kinase inhibitors. To induce apoptosis, cordycepin activates the extrinsic and intrinsic pathways, which promotes reactive oxygen species generation and the downstream activation of kinase cascades. Cordycepin also can activate alternative pathways to cell death such autophagy. In addition, cordycepin can inhibit the pro-metastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the nuclear factor-kappa B and activated protein-1 signaling pathways. In this review, we summarized the variety of action mechanisms by which cordycepin may mediate chemopreventive effects on cancer and discussed the potential of this natural product as a promising therapeutic inhibitor of cancer development.

• Korean Journal of Food Science and Technology
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• v.26 no.4
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• pp.343-347
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• 1994

The effects of low and high-voltage-electrical-stimulation and storing temperature on concentration of adenosine triphosphate (ATP) related compounds were studied in M. Semitendinosus muscles from Korean native cattle. Seven beef carcasses were split, the one side was electrically stimulated for 1 minute by using stimulator adjusted to 400 V/60 Hz as high voltage or to 110 V/60 Hz as low voltage while the other side served as an unstimulated control. Both side samples were incubated at $5^{\circ}C\;and\;15^{\circ}C$ for 3 days. During storage, the concentration of ATP and its breakdown products were measured as a function of time. Significant differences (p<0.05) were observed in the variance of ATP, adenosine diphosphate (ADP) and inosine monophosphate (IMP) levels between low-or high-voltage-electrically stimulated muscles and unstimulated control at just after post-stimulation. The decomposition of adenosine compounds and the production of inosine compounds of low-voltage-electrically stimulated muscles were advanced more slowly than those of high-voltage-treatment muscles. With increasing storage time, the influence of electrical stimulation on changes of ATP related compounds in meat was decreased, but storing temperature begin to affect their concentration. Significant difference in the Hypoxanthine levels (p<0.05) was found of sample stored for 48 hours at $15^{\circ}C$ from samples stored at $5^{\circ}C$ regardless of electrical stimulation treatemt. IMP and inosine values in electrically stimulated muscles, higher than of a control during 72 hours of storage, indicated rapid production of flavor compounds in beef.

• Proceedings of the Ginseng society Conference
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• 1988.08a
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• pp.28-32
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• 1988

Recently, we isolated a toxic substance named 'toxohormone-L' from ascites fluid of patients with various malignant tumors. The toxohormone-L stimulated lipolysis in rat adipocytes and induced anorexia in rats. Both the lipolytic and the anorexigenic actions of toxohormone-L were found to be inhibited by ginsenoside $Rb_2$ in Korean red ginseng. Isolated rat adipocytes are well known to possess opposite pathways of lipid metabolism: lipolysis and lipogenesis. Both of the metabolism respond to various biologically active substances such as epinephrine, ACTH and insulin. Epinephrine and ACTH stimulate lipolysis and insulin accelerates lipogenesis. Recently. Korean red ginseng powder was found to contain adenosine and an acidic substance which inhibited epinephrine-induced lipolysis and stimulated insulin-mediated lipogenesis from added glucose. The chemical structure of this acidic substance is determined to be pyro-glutamic acid (Pyro-Glu), Pyro-Glu exhibits selective modulations toward the opposite metabolic pathways in rat adipocyte; It inhibits the lipolysis but stimulates the lipogenesis. We call these substances (adenosine, Pyro-Glu) 'selective modulators' or 'insulin-like substances'. Based on these results, physiological significances of these substances in Korean red ginseng were discussed.

• Korean Journal of Microbiology
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• v.55 no.2
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• pp.103-111
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• 2019

DNA methylation is involved in diverse processes in bacteria, including maintenance of genome integrity and regulation of gene expression. CcrM, the DNA methyltransferase conserved in Alphaproteobacterial species, carries out $N^6$-adenine or $N^4$-cytosine methyltransferase activities using S-adenosyl methionine as a co-substrate. Celeribacter marinus IMCC12053 from the Alphaproteobacterial group was isolated from a marine environment. Single molecule real-time sequencing method (SMRT) was used to detect the methylation patterns of C. marinus IMCC12053. Gibbs motif sampler program was used to observe the conversion of adenosine of 5'-GANTC-3' to $N^6$-methyladenosine and conversion of $N^4$-cytosine of 5'-GpC-3' to $N^4$-methylcytosine. Exocyclic DNA methyltransferase from the genome of strain IMCC12053 was chosen using phylogenetic analysis and $N^4$-cytosine methyltransferase was cloned. IPTG inducer was used to confirm the methylation activity of DNA methylase, and cloned into a pQE30 vector using dam-/dcm- E. coli as the expression host. The genomic DNA and the plasmid carrying methylase-encoding sequences were extracted and cleaved with restriction enzymes that were sensitive to methylation, to confirm the methylation activity. These methylases protected the restriction enzyme site once IPTG-induced methylases methylated the chromosome and plasmid, harboring the DNA methylase. In this study, cloned exocyclic DNA methylases were investigated for potential use as a novel type of GpC methylase for molecular biology and epigenetics.