As it has been reported that the depolarization induced acetylcholine (ACh) release is modulated by activation of presynaptic A1 adenosine heteroreceptor and various lines of evidence suggest the A2 adenosine receptor is present in the hippocampus. The present study was undertaken to delineate the role of adenosine receptors on the hippocampal ACh release. Slices from the rat hippocampus were equilibrated with (3H)choline and then the release amount of the labelled product, (3H)ACh, which was evoked by electrical stimulation (rectangular pulses, 3 Hz, 2 ms, 24 mA, 5 V/cm-1, 2 min), was measured, and the influence of various adenosine receptor-related agents on the evoked tritium outflow was investigated. And also, the drug-receptor binding assay was performed in order to confirm the presence of A1 and A2 adenosine receptors in the rat hippocampus. N-ethylcarboxamidoadenosine (NECA), a potent adenosine receptor agonist with nearly equal affinity at A1 and A2 adenosine receptors, in concentrations ranging from 1apprx30 muM, decreased the electrically-evoked (3H)ACh release in a concentration-dependent manner without affecting the basal rate of release. And the effect of NECA was significantly inhibited by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 2 micrometer), a selective A1 adenosine receptor antagonist, but was not influenced by 3,7-dimethyl-1-propargylxanthine (DMPX, 5 micrometer, a specific A2 adenosine receptor antagonist. N6-Cyclopentyladenosine (CPA), a selective A1 adenosine receptor agonist, in doses ranging from 0.1 to 10 micrometer, reduced evoked (3H)ACh release in a dose-dependent manner without the change of the basal release. And the effect of CPA was significantly inhibited by 2 micrometer DPCPX treatment. 2-P-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680C), a potent A2 adenosine receptor agonist, in concentrations ranging from 0.1 to 10 micrometer, did not alter the evoked ACh release. In the drug-receptor binding assay, the binding of (3H)2-chloro-N6-Cyclopentyladenosine ((3H)CCPA) to the- A1 adenosine receptor of rat hippocampal membranes was inhibited by CPA (Ki = 1.22 nM), NECA (Ki=10.17 nM) and DPCPX (Ki-161.86 nM), but not by CGS-21680C (Ki=2,380 nM) and DMPX (Ki-22,367 nM). However, the specific binding of (3H)CGS-21680C to the A2 adenosine receptor was not observed. These results suggest that the A1 adenosine heteroreceptor play an important role in evoked ACh release, but the presence of A2 adenosine receptor is not confirmed in this study.
Acetylcholine* ; Adenosine* ; Adenosine-5'-(N-ethylcarboxamide) ; Animals ; Electric Stimulation ; Hippocampus* ; Membranes ; Rats* ; Receptors, Purinergic P1* ; Tritium

BACKGROUND: In two-kidney one clip Goldbaltt hypertensive rats(2K1C GHR), clipped kidney may be exposed to low pressure and unclipped kidney to high pressure. In addition, both kidneys may have a different amount of adenosine which is increased by ischemia and plays an important role for renin release. The aim of this study was to invstigate the responsmiveness for renin release to adenosine agonists and antagonist in clipped and unclipped kidney of 2K1C GHR. METHODS: Emplying kidney slices from both unclipped and unclipped kidney of 2K1C GHR, the alteration by adenosine agonists and antagonist of renin release was studied. RESULTS: The renal renin content and basal renin release from unclipped kidney slices were suppressed, whereas those from clipped kidney were augmented Adenosine Al receptor agonist, cyclohexyladenosne(CHA), phenylisopropyl adenosine(PIA) and adenosine caused a decrease in renin release from clipped kidney slices. Adenosine A2 receptor agonist, NECA, and nonspecific adenosine receptor aganist, 2-chloroadenosine(CA) caused an increase in renin release from clipped kidney slices. Adenosine receptor antagonist, 8-phenyltheophylline(8-PT) caused an increase in renin release from clipped kidney slices. In unclipped kidney, however, the renin release in response to NECA, CA or 8-PT was reversed and the decreasing effect of renin release to CHA and adenosine was slightly inereased. CONCLUSION: These results suggest that the responsiveness of adenosine receptors, which may participate in renin release is modified in clipped and unclipped kidney of 2K1C GHR.
Adenosine* ; Adenosine-5'-(N-ethylcarboxamide) ; Animals ; Hypertension, Renovascular ; Ischemia ; Kidney ; Rats* ; Receptors, Adenosine A2 ; Receptors, Purinergic P1 ; Renin*

Epidural steroid injection (ESI) may be the most widely used interventional procedure in the management of low back pain (LBP). Its use has been supported by more than 45 placebo-controlled studies and dozens of systematic reviews. However the report Pain Reduction Efficacy of Injection Therapy in Chronic LBP by the National Evidence-Based Collaborating Agency (NECA) in 2010 is seen to have mis-concluded that ESI is not effective in the management of chronic LBP. The NECA report contains various descriptive and statistical errors. In this review, we have attempted to correct the errors in the NECA report. We also inform the rationale and evidence of ESI by the review of recent meta-analysis and work to inspire a proper use of ESI in the Republic of Korea.
Adenosine-5'-(N-ethylcarboxamide)* ; Evidence-Based Practice ; Low Back Pain ; Meta-Analysis as Topic ; Republic of Korea

BACKGROUND/AIMS: Adenosine is an endogenous modulator of nociception. Its role in visceral nociception, particularly in visceral hyperalgesia, has not been studied. The aim of this study was to determine the effects of adenosine receptor agonists in a model of visceral hyperalgesia. METHODS: The visceromotor response (VMR) in rats to colorectal distension (CRD; 80 mmHg, 20 seconds) was quantified by electromyographic recordings from the abdominal musculature. Three hours after the intracolonic administration of zymosan (25 mg/mL, 1 mL), VMRs to CRD were measured before and after either subcutaneous or intrathecal administration of an adenosine receptor agonist. RESULTS: Subcutaneous injection of 5'-N-ethylcarboxyamidoadenosine (NECA; an A1 and A2 receptor agonist), R(-)-N6-(2-phenylisopropyl)-adenosine (R-PIA; a selective A1 receptor agonist), or CGS-21680 hydrochloride (a selective A2a receptor agonist) dose-dependently (10-100 mg/kg) attenuated the VMR to CRD, although hindlimb weakness occurred at the higher doses tested. Intrathecal administration of NECA or R-PIA dose-dependently (0.1-1.0 microgram/kg) decreased the VMR, whereas CGS-21680 hydrochloride was ineffective over the same concentration range. Higher intrathecal doses of the A1/A2 receptor agonist NECA produced motor weakness. CONCLUSIONS: Adenosine receptor agonists are antihyperalgesic, but also produce motor weakness at high doses. However, activation of the spinal A1 receptor significantly attenuates the VMR to CRD without producing motor weakness.
Adenosine ; Adenosine-5'-(N-ethylcarboxamide) ; Animals ; Hindlimb ; Hyperalgesia ; Injections, Subcutaneous ; Nociception ; Purinergic P1 Receptor Agonists ; Rats ; Receptors, Purinergic P1 ; Zymosan

To establish an appropriate policy for robotic surgery in Korea, the National Evidence-based Collaborating Agency (NECA) and the Korean Society of Health Policy and Administration held a round-table conference (RTC) to gather opinions through a comprehensive discussion of scientific information in gastric cancer. The NECA RTC is a public discussion forum wherein experts from diverse fields and members of the lay public conduct in-depth discussions on a selected social issue in the health and medical field. For this study, representatives from the medical field, patient groups, industry, the press, and policy makers participated in a discussion focused on the medical and scientific evidence for the use of robotic surgery in gastric cancer. According to the RTC results, robotic surgery showed more favorable results in safety and efficacy than open surgery and it is similar to laparoscopy. When the cost-effectiveness of robotic surgery and laparoscopy is compared, robotic surgery costs are higher but there was no difference between the two of them in terms of effectiveness (pain, quality of life, complications, etc.). In order to resolve the high cost issue of the robotic surgery, a proper policy should be implemented to facilitate the development of a cost-effective model of the robotic surgery equipment. The higher cost of robotic surgery require more evidence of its safety and efficacy as well as the cost-effectiveness issues of this method. Discussions on the national insurance coverage of robotic surgery seems to be necessary in the near future.
Adenosine-5'-(N-ethylcarboxamide) ; Administrative Personnel ; Consensus* ; Health Policy ; Humans ; Insurance Coverage ; Korea ; Laparoscopy ; Quality of Life ; Stomach Neoplasms*

Evidence for the existence of at least two subclasses of renal adenosine receptors has been presented. N-6-cyclohexyladenosine (CHA) is a relatively selective A-1 adenosine agonists, whereas 5'-N-ethylcarboxamidoadenosine (NECA) acts as a preferential agonist of A-2 adenosine receptor. N6-(L-2-phenylisopropyl)-adenosine (PIA) almost unselectively activates both A-1 and A-2 adenosine receptors at micromolar concentrations. During the characterization of adenosine receptor in the kidney, we have discovered a novel phenomenon, that is, an intramuscular administration of CHA for 3 days caused a diuresis and a suppression of urinary concentrating ability. To further characterize this novel phenomenon, an intramuscular administration of adenosine and other adenosine angonists, PIA and NECA, and prior treatment of adenosine antagonists, caffeine, theophylline and 1,3-diethyl-8-phenyl-xanthine (DPX) were performed. Systemic administration of CHA, PIA, and NECA for 3 days caused a suppression in heart rate, blood pressure and general motor activity without change in rectal temperature. Systemic administration of CHA, 0.5, 1 and 2 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and decrease in urinary osmolarity and free water reabsorption. This phenomenon was reversible and repeatable. Administration of adenosine (40 mg/kg/day) produced no apparent effect on the renal function, whereas PIA (2 mg/kg/day) produced an similar effect to CHA on the renal function. Systemic administration of NECA, 0.025, 0.05 and 0.25 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and dose-dependent increases in excreted amount of creatinine, urinary osmolarity and free water reabsorption. These renal effects of adenosine agonist were maximum at second day during the drug administration. In terms of increase in urine volume and the suppression of urinary concentrating ability, NECA was potent than CHA. Prior treatment of caffeine (50 mg/kg/day) or theophylline (50 mg/kg/day) abolished the diuretic effect of, CHA, whereas DPX (50 mg/kg/day) did not affect the CHA effect. CHA, 0.5 mg/kg/day, produced no change in plasma renin activity and plasma levels of aldosterone, epinephrine, and norepinephrine. These results suggest that this novel phenomenon produced by an activation of renal adenosine receptors plays an important role in urinary concentrating mechanism.
Adenosine* ; Adenosine-5'-(N-ethylcarboxamide) ; Aldosterone ; Blood Pressure ; Caffeine ; Creatinine ; Diuresis ; Diuretics ; Epinephrine ; Heart Rate ; Kidney ; Motor Activity ; Norepinephrine ; Osmolar Concentration ; Plasma ; Receptors, Purinergic P1 ; Renin ; Theophylline ; Water

As it has been reported that the depolarization induced acetylcholine (ACh) release is modulated by activation of presynaptic A-1 adenosine heteroreceptor and various evidence suggest that indicate the A-2 adenosine receptor is present in the striatum, this study was undertaken to delineate the role of adenosine receptors on the striatal ACh release. Slices from the rat striatum were equilibrated with (3H)choline and then the release amount of the labelled product, (3H)ACh, which was evoked by electrical stimulation (rectangular pulses, 3 Hz, 2 ms, 24 mA, 5 Vcm-1, 2 min), was measured, and the influence of various agents on the evoked tritium outflow was investigated. And also, quantitative receptor autoradiography and drug-receptor binding assay were performed in order to confirm the presence and characteristics of A-1 and A-2 adenosine receptors in the rat striatum. Adenosine (10 ~ 100 micrometer) and N-6-cyclopentyladenosine (CPA, 1 ~ 100 micrometer) decreased the (3H)ACh release in a dose-dependent manner without changing the basal rate of release in the rat striatum. The reducing effects of ACh release by adenosine and CPA were abolished by 8-cyclopentyl-1,3-dipropy-lxanthine (DPCPX, 2 micrometer), a selective A-1 adenosine receptor antagonist, treatment. The effect of adenosine was potentiated markedly by 3,7-dimethyl-1-propargylxanthine (DMPX, 10 micrometer), a specific A-2 adenosine receptor antagonist. 2-P-(2-carboxyethyl)phenethylamimo-5'-N- ethylcarboxamidoadenosine hydrochloride (CGS-21680C), in concentrations ranging from 0.01 to 10 micrometer, a recently introduced potent A-2 adenosine receptor agonist, increased the(3 H)ACh release in a dose related fashion without changing the basal rate of release. These effects were completely abolished by DMPX (10 micrometer). In autoradiogaphy experiments, (3H)2-chloro-N-6-cyclopentyladenosine ((3 H)CCPA) bindings were highly localized in the hippocampus and the cerebral cortex. Additionally, lower levels of binding were found in the striatum. However, (3H)CGS-21680C bindings were highly localized in the striatal region with the greatest density of binding found in the caudate nucleus and putamen. Lower levels of binding were also found in the nucleus accumbens and olfactory tubercle. In drug-receptor binding assay, binding of (3H)CCPA to A-1 adenosine receptors of rat striatal membranes was inhibited by CPA (K-i = 1.6nM) and N-ethylcarboxamidoadenosine (NECA, K-i = 12.9 nM), but not by CGS-21680C (K-i = 2609.2 nM) and DMPX (K-i = 19,386 nM). In contrast, (3H)CGS-21680C binding to A-2 adenosine receptors was inhibited by CGS-21680C (K-i = 47.6 rim) and NECA (K-i = 44.9 nM), but not by CPA (K-i = 2099.2 nM) and DPCPX (K-i = 19,207 nM). The results presented here suggest that both types of A-1 and A-2 adenosine heteroreceptors exist and play an important role in ACh release in the rat striatal cholinergic neurons.
Acetylcholine* ; Adenosine* ; Adenosine-5'-(N-ethylcarboxamide) ; Animals ; Autoradiography ; Caudate Nucleus ; Cerebral Cortex ; Cholinergic Neurons ; Electric Stimulation ; Hippocampus ; Membranes ; Nucleus Accumbens ; Olfactory Pathways ; Putamen ; Rats* ; Receptors, Purinergic P1* ; Tritium

A2B adenosine receptor is involved in the control of mast cell degranulation, interleukin-8 synthesis and cell growth. A2B adenosine receptor antagonists may serve as novel drugs for asthma, Alzheimer' s disease, cystic fibrosis and type-II diabetes. Therefore, seeking for the highly selective A2B adenosine receptor antagonists has been one of great interest. The molecular basis, structure-activity relationship of selective A2B adenosine receptor antagonists and their interactions with A2B adenosine receptor were reviewed.
Adenosine ; pharmacology ; Adenosine A2 Receptor Antagonists ; Adenosine A3 Receptor Antagonists ; Adenosine-5'-(N-ethylcarboxamide) ; pharmacology ; therapeutic use ; Animals ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; drug therapy ; Humans ; Pulmonary Artery ; drug effects ; Structure-Activity Relationship ; Xanthines ; pharmacology

Numerous studies have shown that adenosine or adenosine agonists can stimulate angiogenesis. However, the effect of caffeine (a known adenosine receptor antagonist) on angiogenesis has not been previously studied. Accordingly, this study was undertaken to examine the effect of caffeine on angiogenesis and to clarify the mechanism involved. Chick chorioallantoic membrane assays were used to investigate the effect of caffeine on angiogenesis and proliferation assays using human umbilical vein endothelial cells (HUVECs), were used to study its effects on specific aspects of angiogenesis. The expressions of caspase-3 and Bcl-2 were examined by western blotting, immunofluorescence staining was used to identify HUVEC morphological changes, and fluorescence activated cell sorting (FACS) and DAPI staining were used to detect HUVEC apoptosis. Caffeine was found to inhibit blood vessel formation dose-dependently and to inhibit the proliferation of HUVECs time- and dose-dependently. FACS analysis and DAPI staining showed that inhibitory effect of caffeine on HUVEC proliferation was the result of apoptosis and the up-regulation of thrombospondin-1 (TSP-1). Furthermore, TSP-1 levels were down-regulated by NECA but were unaffected by CGS21680, indicating that caffeine regulated TSP-1 expression via adenosine A2B receptor. In addition, caffeine up-regulated caspase-3 and down-regulated Bcl-2 at the protein level. These results suggest that the inhibitory effect of caffeine on angiogenesis is associated, at least in part, with its induction of endothelial cell apoptosis, probably mediated by a caspase-3 dependent mechanism.
Adenosine ; Adenosine-5'-(N-ethylcarboxamide) ; Apoptosis ; Blood Vessels ; Blotting, Western ; Caffeine ; Caspase 3 ; Chorioallantoic Membrane ; Endothelial Cells ; Flow Cytometry ; Fluorescent Antibody Technique ; Glycosaminoglycans ; Human Umbilical Vein Endothelial Cells ; Indoles ; Phenethylamines ; Receptor, Adenosine A2B ; Receptors, Purinergic P1 ; Thrombospondin 1 ; Up-Regulation

The National Evidence-based Healthcare Collaborating Agency (NECA), an institution for health technology assessment in Korea, has used public solicitation of research topics since its establishment in 2009. This creates a necessity for examining whether a given research topic was selected to be considered when prioritizing healthcare technology assessment and distributing healthcare resources. This study aimed to investigate the relationship between the research topics suggested to NECA and the disease burden in Korea. To find the correlation between disease burden and 1,112 suggested topics and 91 performed topics that were classified by Human Research Classification System a linear auxiliary trend line and scatter plot were constructed using disability-adjusted life years (DALYs), and Pearson's correlation coefficients were calculated. The results suggested that cancer was most common, followed by cardiovascular diseases, among suggested research topics and research topics performed by NECA, as well as in terms of the ratio of performed to suggested topics. The correlation between research topic and disease burden index indicated a strong correlation with DALYs and years of life lost (YLLs). However, years lived with disability and research topic had no relationship. Suggested topics showed a greater correlation with YLLs than DALYs, whereas performed topics showed a greater correlation with DALYs than YLLs, showing that despite the fact that the diseases with a high burden from morbidity were appropriately considered with respect to selecting research topics, a statistically significant difference was not found. As the first Korean study to assess the correlation between research topics and disease burden, our results will be used as base data for prioritizing the allocation of healthcare resources in the future.
Adenosine-5'-(N-ethylcarboxamide) ; Biomedical Technology* ; Cardiovascular Diseases ; Classification ; Cost of Illness ; Delivery of Health Care ; Evidence-Based Practice ; Humans ; Korea ; Technology Assessment, Biomedical*