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At least 19 recordsLinked to original sources
PubMed1986

Uptake of free adenosine and adenosine from adenosine monophosphate by human peripheral blood lymphocytes: possible kinetic role for ecto-5'-nucleotidase in the regulation of intracellular adenosine.

The role of 5'-nucleotidase in the uptake of adenosine from AMP was investigated in lymphocytes from normal subjects and patients with common variable hypogammaglobulinaemia (CVH) and chronic lymphatic leukaemia (CLL). At physiological pH, the Km values for the uptake of adenosine and of adenosine from AMP by intact cells were one order of magnitude higher than the Km values for 5'-nucleotidase. The Vmax values for the hydrolysis of AMP by 5'-nucleotidase were two orders of magnitude greater than for the uptake of adenosine itself or the uptake of adenosine from AMP by normal lymphocytes. 5'-Nucleotidase activity is clearly not rate-limiting in normal lymphocytes for uptake of adenosine from AMP in steady state conditions. Patients with common variable hypogammaglobulinaemia showed a low Vmax for 5'-nucleotidase assayed at pH 7.4 in intact cells as compared to values from control subjects. Michaelis constants (Km) for the uptake of free adenosine and adenosine from AMP as well as 5'-nucleotidase were similar compared to those obtained for controls. The uptake of adenosine moiety from AMP in CLL lymphocytes with a low Vmax for 5'-nucleotidase was also reduced, although not to the same extent as the reduction in 5'-nucleotidase activity. One CLL patient with supranormal levels of 5'-nucleotidase activity showed elevated uptake of adenosine moiety from AMP and of free adenosine. These results suggest that 5'-nucleotidase can influence the salvage of purine by lymphocytes from extracellular nucleotides but only when the enzyme activity is greatly reduced.

5'-Nucleotidase↗
PubMed1978

A calcium ion-dependent adenosine triphosphate pyrophosphohydrolase in plasma membrane from rat liver. Demonstration that the adenosine triphosphate analogues adenosine 5'-[betagamma-imido]triphosphate and adenosine 5'-[betagamma-methylene]-triphosphate are substrates for the enzyme.

An ATP pyrophosphohydrolase in a rat liver plasma-membrane subfraction was studied with respect to specific Ca2+ activation of the beta-phosphate bond hydrolysis. ATP and, in addition, adenosine 5'-[betagamma-imido]triphosphate and adenosine 5'-[betagamma-methlylene]triphosphate were substrates for Ca2+-stimulated enzymic hydrolysis of the beta-phosphate bond. A 15-fold activation was observed by raising the free Ca2+ concentration from 10(-7) to 10(-5) M. Mg2+ had little effect. Solubilization in 1% deoxycholate and partial purification on a sucrose density gradient resulted in a 5-fold increase in specific activity with unaltered Ca2+-stimulation pattern. The possible importance of the enzyme in Ca2+ transport is discussed.

Adenosine Triphosphatases↗
PubMed1992

Interstitial adenosine with dipyridamole: effect of adenosine receptor blockade and adenosine deaminase.

Dipyridamole is proposed to increase coronary blood flow (CBF) by inhibition of adenosine uptake into cells, resulting in an increase in interstitial fluid (ISF) adenosine and an adenosine-mediated vasodilation. The purpose of this study was to determine the changes in CBF and ISF adenosine, inosine, and hypoxanthine during dipyridamole infusion in the absence or presence of adenosine receptor blockade or adenosine deaminase. To sample cardiac ISF, cardiac microdialysis probes were implanted in the left ventricular myocardium of chloralose-urethan-anesthetized dogs and perfused with Krebs-Henseleit buffer. The metabolite concentration in the effluent dialysate was used as an index of intramyocardial ISF metabolite concentration. In response to dipyridamole, CBF and dialysate adenosine concentration increased 4.4-fold and 2.2-fold, respectively, whereas dialysate inosine was unchanged and dialysate hypoxanthine decreased 50%. Adenosine receptor blockade, achieved by intracoronary 8-(p-sulfophenyl)theophylline infusion, attenuated the increase in CBF induced by dipyridamole without changing dialysate adenosine concentration. Adenosine deaminase fully attenuated the dipyridamole-induced increases in CBF and dialysate adenosine. These results demonstrate that dipyridamole increases ISF adenosine in the dog and suggest that adenosine is the sole mediator of dipyridamole-induced coronary vasodilation.

Adenosine↗
PubMed1978

Adenosine kinase as a new selective marker in somatic cell genetics: isolation of adenosine kinase--deficient mouse cell lines and human--mouse hybrid cell lines containing adenosine kinase.

A new selective system for isolating somatic cell hybrids, using adenosine kinase as the selective marker, has been developed. The selective medium for forward selection (to select for cells containing adenosine kinase) contains alanosine, adenosine and uridine. To survive in the presence of alanosine, cells must have adenosine kinase in order to utilize exogenous adenosine as the sole source of AMP. Uridine is added to the selective medium to prevent the toxic effects of adenosine on cultured mammalian cells. The selective medium for reverse selection (to select for cells lacking adenosine kinase) contains 2-fluoroadenosine, an analogue of adenosine, which is converted to a toxic nucleotide by the action of adenosine kinase. Mouse mutant cell lines deficient in adenosine kinase have been derived. Human--mouse hybrid cells containing the kinase have been prepared from one of these mutant lines. Karyotype data of these hygrid lines and their adenosine kinase-minus sublines are consistent with assignment by others of the human gene for adenosine kinase on chromosome 10.

Adenosine↗
PubMed1978

Activities and some properties of 5'-nucleotidase, adenosine kinase and adenosine deaminase in tissues from vertebrates and invertebrates in relation to the control of the concentration and the physiological role of adenosine.

1. The maximal activities of 5'-nucleotidase, adenosine kinase and adenosine deaminase together with the Km values for their respective substrates were measured in muscle, nervous tissue and liver from a large range of animals to provide information on the mechanism of control of adenosine concentration in the tissues. 2. Detailed evidence that the methods used were optimal for the extraction and assay of these enzymes has been deposited as Supplementary Publication SUP 50088 (16pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K.,from whom copies can be obtained on the terms indicated in Biochem. J. (1978), 169, 5. This evidence includes the effects of pH and temperature on the activities of the enzymes. 3. In many tissues, the activities of 5'-nucleotidase were considerably higher than the sum of the activities of adenosine kinase and deaminase, which suggests that the activity of the nucleotidase must be markedly inhibited in vivo so that adenosine does not accumulate. In the tissues in which comparison is possible, the Km of the nucleotidase is higher than the AMP content of the tissue, and since some of the latter may be bound within the cell, the low concentration of substrate may, in part, be responsible for a low activity in vivo. 4. In most tissues and animals investigated, the values of the Km of adenosine kinase for adenosine are between one and two orders of magnitude lower than those for the deaminase. It is suggested that 5'-nucleotidase and adenosine kinase are simultaneously active so that a substrate cycle between AMP and adenosine is produced: the difference in Km values between kinase and deaminase indicates that, via the cycle, small changes in activity of kinase or nucleotidase produce large changes in adenosine concentration. 5. The activities of adenosine kinase or deaminase from vertebrate muscles are inversely correlated with the activities of phosphorylase in these muscles. Since the magnitude of the latter activities are indicative of the anaerobic nature of muscles, this negative correlation supports the hypothesis that an important role of adenosine is the regulation of blood flow in the aerobic muscles.

Adenosine↗
PubMed1978

Effect of adenosine, adenosine analogues and drugs inhibiting adenosine inactivation on lipolysis in rat fat cells.

It has been suggested that adenosine may be a physiologically important modulator of lipolysis. In the present study it was found that adenosine inhibited lipolysis stimulated by low (0.03 micrometer) concentrations of noradrenaline (NA). Lipolysis stimulated by higher concentrations (0.3 and 3 micrometer) of NA was inhibited to a minor degree or not at all. Theophylline (1 micromete)-induced lipolysis was inhibited by adenosine (IC50 approximately 10 micrometer). Inhibition of theophylline-induced lipolysis was tested for several analogues of adenosine. Some N6-substituted adenosine analogues and 2-Cl-adenosine were more potent inhibitors. Adenine-nucleotides (ATP, ADP, AMP) were about equipotent with adenosine. Several adenosine analogues, including its breakdown products were considerably less potent or ineffective. None of the analogues tested inhibited the action of adenosine. Dipyridamol, dilazep and papaverine, which inhibit the uptake of adenosine into cells, caused only a slight enhancement of the antilipolytic effect of adenosine. None of the analogues inhibited the effect of adenosine. It is concluded that adenosine can inhibit lipolysis due to low, "physiological" concentrations of noradrenaline and of low concentration of theophylline via an action on a receptor structure on the cell surface which exhibits structural specificity.

Adenosine↗
PubMed1990

Localization of adenosine deaminase and adenosine deaminase complexing protein in rabbit heart. Implications for adenosine metabolism.

The distribution of adenosine deaminase and adenosine deaminase complexing protein in rabbit heart has been compared using immunohistochemical staining procedures. Sections (4-5 microns) of tissue fixed in Clarke's solution or paraformaldehyde and embedded in paraffin were stained by the peroxidase anti-peroxidase method for adenosine deaminase or complexing protein, using affinity purified antibodies. Staining for adenosine deaminase and complexing protein was observed in the central myocardium of all heart chambers. Adenosine deaminase was detected in endothelial cells of blood vessels and adjacent pericytes. The nuclei of arteries stained heavily for adenosine deaminase, whereas those of venules and small veins, although positive, stained much more lightly. The cytoplasm of blood vessel endothelial cells and smooth muscle cells of the tunica media were also weakly positive for adenosine deaminase. Endothelial cells of the endocardium and epicardium did not stain. Randomly distributed mononuclear inflammatory cells and interstitial connective tissue fibroblasts were also negative for adenosine deaminase. These results raise the possibility that endothelial cells containing adenosine deaminase could serve as a metabolic barrier preventing the free exchange of plasma and interstitial adenosine. Positive staining for complexing protein was restricted to blood vessel endothelial cells, especially cytoplasmic processes. Colocalization experiments carried out with biotinylated primary antibodies indicate that some vessels are positive for both adenosine deaminase and complexing protein. This is the first experimental evidence of possible in situ association of adenosine deaminase and complexing protein.

Adenosine↗
PubMed1988

Adenosine receptor-mediated effects by nonmetabolizable adenosine analogs in preovulatory rat granulosa cells: a putative local regulatory role of adenosine in the ovary.

The influence of nonmetabolizable adenosine analogs on cAMP production was investigated in preovulatory rat granulosa cells. 5'-(N-ethyl)Carboxamido-adenosine (NECA), a stimulatory A2-adenosine receptor agonist, stimulated cAMP accumulation, and NECA and 2-chloro-adenosine also potentiated the response to FSH. The adenosine receptor antagonist 8-phenyltheophylline antagonized the effect of NECA, shown by a shift in the dose-response curve to the right. The stimulatory effect of NECA was also seen in an ovarian membrane preparation, where NECA stimulated adenylate cyclase in both the presence and absence of FSH. The stimulatory effect of NECA was also decreased by 8-phenyltheophylline in this preparation. The A1-receptor agonists N6-(R-phenyl-isopropyl)-adenosine (R-PIA) and N6-(S-phenyl-isopropyl)-adenosine (S-PIA) both inhibited FSH-stimulated cAMP accumulation. The inhibitory effects of R-PIA and S-PIA, but not the stimulatory effects of NECA, could be counteracted by dipyridamole, a nucleoside transport inhibitor. Furthermore, R-PIA and S-PIA inhibited adenosine uptake into granulosa cells. Thus, the inhibitory effects of R-PIA and S-PIA are not likely to be mediated via membrane-bound inhibitory A1-adenosine receptors. Neither the stimulatory effects of NECA nor the inhibitory effects of R- and S-PIA could be attributed to changes in ATP levels, since the ATP levels were unaffected by these analogs. The results of this study indicate the existence of stimulatory A2-adenosine receptors in preovulatory rat granulosa cells and suggest a membrane-associated modulatory role of adenosine in preovulatory granulosa cells.

2-Chloroadenosine↗
PubMed1975

Synthesis of adenosine triphosphate and exchange between inorganic phosphate and adenosine triphosphate in sodium and potassium ion transport adenosine triphosphatase.

Radioactive adenosine triphosphate was synthesized transiently from adenosine diphosphate and radioactive inorganic phosphate by sodium and potassium adenosine triphosphatase from guinea pig kidney. In a first step, K+-sensitive phosphoenzyme was formed from radioactive inorganic phosphate in the presence of magnesium ion and 16 mM sodium ion. In a second step the addition to the phosphoenzyme of adenosine diphosphate with a higher concentration of sodium ion produced adenosine triphosphate. Recovery of adenosine triphosphate from the phosphoenzyme was 10 to 100% in the presence of 96 to 1200 mM sodium ion, respectively. Potassium ion (16mM) inhibited synthesis if added before or simultaneously with the high concentration of sodium ion but had no effect afterward. The half-maximal concentration for adenosine diphosphate was about 12 muM. Ouabain inhibited synthesis. The ionophore gramicidin had no significant effect on the level of phosphoenzyme nor on the rate nor on the extent of synthesis of adenosine triphosphate. The detergent Lubrol WX reduced the rate of phosphoenzyme break-down and the rate of synthesis but did not affect the final recovery. Phospholipase A treatment inhibited synthesis. In a steady state, the enzyme catalzyed a slow ouabain-sensitive incorporation or inorganic phosphate into adenosine triphosphate. These results and other suggest that binding of sodium ion to a low affinity site on phosphoenzyme formed from inorganic phosphate is sufficient to induce a conformational change in the active center which permits transfer of the phosphate group to adenosine diphosphate.

Adenosine Triphosphatases↗
PubMed1991

Myocardial glucose utilization. Failure of adenosine to alter it and inhibition by the adenosine analogue N6-(L-2-phenylisopropyl)adenosine.

The effects of adenosine and the nonmetabolizable adenosine analogue N6-(L-2-phenylisopropyl)adenosine (PIA) on glucose transport or metabolism were determined in purified myocardial sarcolemmal vesicles, isolated cardiocytes, and perfused hearts. Adenosine (100 microM) did not affect hexose transport in myocytes. Also, adenosine deaminase, added to metabolize adenosine to inosine, did not alter transport of hexose into myocytes regardless of whether or not insulin was present. In contrast, PIA effectively inhibited 3-O-methyl-D-glucose uptake in myocytes even during insulin stimulation. PIA inhibited D-glucose-specific transport in both rat and bovine cardiac sarcolemmal vesicles (Ki = 26 microM at [D-glucose] = 5 mM). However, insulin did not affect glucose transport in sarcolemmal vesicles, which implies that receptor-coupled processes probably are not intact in this preparation. Thus, inhibition of PIA may not be receptor mediated. Also, PIA inhibited binding of cytochalasin B to bovine cardiac sarcolemmal vesicles, which supports the idea that PIA inhibits glucose flux by binding to the glucose transporter. To determine if adenosine altered glucose metabolism rather than transport, we measured the rate of 3H2O production from metabolism of D-[2-3H]glucose in paced rat hearts ([D-glucose] = 5.5 mM, [pyruvate] = 0.2 mM) perfused with a range of PIA or adenosine concentrations with or without 0.01 microM insulin. Adenosine (0.01-100 microM) in the presence or absence of insulin increased coronary flow but did not change glycolytic rates. Similar results were obtained with PIA (no insulin) rather than adenosine in the perfusate. However, with glucose as the only exogenous substrate, 100 microM PIA inhibited glycolysis by approximately 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1988

Substrate inhibition of adenosine phosphorylation in adenosine deaminase deficiency and adenosine-mediated inhibition of PP-ribose-P dependent nucleotide synthesis in hypoxanthine phosphoribosyltransferase deficient erythrocytes.

The metabolism of adenosine and its effects on phosphoribosylpyrophosphate, PP-ribose-P, dependent nucleotide synthesis were studied using erythrocytes from patients with adenosine deaminase and hypoxanthine phosphoribosyltransferase deficiency as models. The phosphorylation of adenosine was progressively inhibited by concentrations of adenosine greater than 1 mumol L-1 for control and ADA deficient erythrocytes. There was essentially no initial rate of phosphorylation at 30 mumol L-1 adenosine. Adenosine, 1 mumol L-1, also caused a 60% reduction in PP-ribose-P concentration in ADA deficient erythrocytes. For HPRT deficient erythrocytes in which ADA activity was blocked by coformycin, 10 mumol L-1 inosine stimulated PP-ribose-P dependent nucleotide synthesis from adenine, whereas, 10 mumol L-1 adenosine inhibited nucleotide synthesis. These observations suggest that adenosine phosphorylation and PP-ribose-P dependent nucleotide synthesis are inhibited under conditions in which adenosine accumulates, such as in hereditary or pharmacologically induced ADA deficiency.

Adenosine↗
PubMed1975

Studies on mammalian ribonucleotide reductase inhibition by pyridoxal phosphate and the dialdehyde derivatives of adenosine, adenosine 5'-monophosphate, and adenosine 5'-triphosphate.

Ribonucleotide reductase activity in a partially purified enzyme preparation from Ehrilich tumor cells was inhibited by the dialdehyde derivatives of adenosine, 5-adenylic acid, and adenosine 5-triphosphate (prepared by the periodate oxidation of adenosine 5-adenylic acid, and adenosine 5-triphosphate). The borohydride-reduced derivative of periodate-oxidized adenosine was not inhibitory to the ribonucleotide reductase activity, showing that the aldehyde moiety was important in the inhibitory interactions of these compounds. This suggested the formation of a Schiff base between the dialdehyde derivative and an amino group (presumably, the epsilon-amino group of lysine). Pyridoxal phosphate, which is known to inhibit enzymes that have lysyl residues in the catalytic or allosteric sites, was an inhibitor of ribonucleotide reductase. Pyridoxal, pyridoxamine phosphate, pyridoxamine, and pyridoxine were not inhibitors. Borohydride reduction of the enzyme in the presence of pyridoxal phosphate produced a protein fraction that had little reductase activity remaining. The inhibition by pyridoxal phosphate was not influenced by increasing the substrate concentration (cytidine 5-diphosphate or adenosine 5-diphosphate), but was diminished by increasing the ratio of allosteric effector to pyridoxal phosphate concentrations, suggesting an interaction of pyridoxal phosphate at the regulatory site of ribonucleotide reductase. The addition of adenosine 5-triphosphate to the pyridoxal phosphate-enzyme mixture, which was subsequently treated with borohydride, partially prevented the inhibition by pyridoxal phosphate. Heat treatment of the ribonucleotide reductase enzyme preparation in the presence of pyridoxal phosphate protected the enzyme against loss of cytidine 5-diphosphate and adenosine 5-diphosphate reductase activities.

Adenosine↗
PubMed1985

Regulation of macrophage lysosomal secretion by adenosine, adenosine phosphate esters, and related structural analogues of adenosine.

Zymosan particle-stimulated beta-galactosidase secretion by mouse peritoneal macrophages was found to be inhibited by micromolar concentrations of adenosine, AMP, ADP, and ATP. Inhibition by all four agents was increased to approximately 80% by adding erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; 10 microM) an adenosine deaminase inhibitor, to the incubation medium. The inhibition of lysosomal enzyme secretion by ATP, ADP, and AMP was reversed by adding alpha, beta -methylene ADP (100 microM), a 5'-nucleotidase inhibitor, to the incubation medium. Inhibition by adenosine, however, was unaffected by alpha, beta -methylene ADP indicating that the inhibition by AMP, ADP, and ATP only occurred after they had been converted to adenosine by cell surface phosphohydrolases, including 5'-nucleotidase. Theophylline, a competitive antagonist of the binding of adenosine to plasma membrane adenosine receptors, failed to reverse the inhibitory effect of adenosine indicating the probable site of adenosine action to be intracellular. Other purine nucleosides, e.g., guanosine, and several purine and ribosemodified structural analogues of adenosine also inhibited zymosan-stimulated beta-galactosidase secretion, while xanthosine and certain pyrimidine nucleosides, e.g., thymidine, were inactive in this respect.

Adenine↗
PubMed1989

Rat adipose tissue adenosine sensitivity and adenosine content after subcutaneous administration of N6-(phenylisopropyl)adenosine.

Injections of N6-(phenylisopropyl)adenosine, a nonmetabolizable adenosine A1 receptor agonist, desensitized rat adipocytes to the drug in 20 h. Lipolysis stimulated by 2 mumol/l DL-isoproterenol was inhibited markedly less by N6-(phenylisopropyl)adenosine in adipocytes isolated from treated than control animals (P less than 0.01). Glucose uptake was more responsive to N6-(phenylisopropyl)adenosine in adipocytes from control than treated animals (P less than 0.02). Adenosine content was the same in adipose tissue of control and treated animals. The number of adenosine binding sites was not significantly lower in treated compared with control animals (1580 +/- 279 and 1988 +/- 575 fmol/mg protein; mean +/- SEM). There was no change in receptor affinity (Kd = 10 nmol/l in both groups). There was no decrease in the amounts of the inhibitory guanine nucleotide binding protein (Gi) alpha subunits as studied by pertussis toxin catalyzed ADP-ribosylation. It is concluded that desensitization to N6-(phenylisopropyl)adenosine can be observed without changes in the adenosine receptor status or decrease in the amount of inhibitory guanine nucleotide binding protein and that adipose tissue adenosine content is not changed by the agonist treatment.

Adenosine↗
PubMed1987

Potentiation of adenosine triphosphate-induced contractile responses of the guinea-pig isolated vas deferens by adenosine monophosphate and adenosine 5'-monophosphorothioate.

The effects of incubating the guinea-pig isolated vas deferens in the presence of adenine nucleotides (adenosine triphosphate, ATP; adenosine diphosphate, ADP; and adenosine monophosphate, AMP), or in the presence of their phosphorothioate analogues (adenosine 5'-O-(3-thiotriphosphate), ATP gamma S; adenosine 5'-O-(2-thiodiphosphate), ADP beta S; and adenosine 5'-monophosphorothioate, AMP alpha S), on contractile responses to ATP were compared. After challenge with a low (1 microM) or high (300 microM) concentration of ATP to obtain control responses, one vas deferens of a pair was incubated for 5 min with one of the adenine nucleotides, while the contralateral preparation was incubated with the corresponding phosphorothioate analogue. At the conclusion of the incubation the preparations were challenged again with ATP. Incubation with AMP or AMP alpha S resulted in a transient potentiation of responses to 1 microM and 300 microM ATP. The potentiation following incubation with AMP alpha S was larger than that produced by AMP. After incubation with ADP, ADP beta S, ATP and ATP gamma S, responses to 1 microM ATP were decreased, while those to 300 microM ATP were unaffected. Thus, incubation with AMP and AMP alpha S results in potentiation, rather than inhibition, of ATP-induced responses. On the other hand, 5'-diphosphate, 5'-triphosphate, 5'-O-(2-thiodiphosphate) and 5'-O-(3-thiotriphosphate) moieties on adenosine have no effect or cause autoinhibition. These results indicate that AMP exerts a potentiating effect on reactivity to exogenous ATP. AMP arising from the enzymatic degradation of ATP might modulate the level of response to ATP released endogenously as a cotransmitter.

Adenosine Monophosphate↗
PubMed1989

Adenosine stimulates adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate accumulation in rat pinealocytes: evidence for a role for adenosine in pineal neurotransmission.

Adenosine produces a concentration-dependent increase in pinealocyte cAMP (EC50, approximately 0.3 nM) and cGMP accumulation (EC50, approximately 0.7 nM). Maximal increases in both nucleotides are evident 10 min after treatment; 1 h later values return to pretreatment levels. Concentration-dependent effects on cAMP are also observed with N6-(L-2-phenylisopropyl)adenosine (EC50, approximately 0.75 nM), 5'-N-ethylcarboxy aminoadenosine (EC50, approximately 0.75 nM), and 2-chloroadenosine (EC50, approximately 2.0 nM); the EC50 values for stimulation of cGMP with these agents are higher by a factor of 2-10. In the case of 5'-N-ethylcarboxy amidoadenosine, the concentration-response curve is biphasic, with a significant effect evident within the range of 1-100 pM. The stimulatory nature of this response and the relative potency of the agonists tested are consistent with the involvement of an A2-like adenosine receptor. Comparison of adenosine and the selective beta-adrenergic agonist isoproterenol indicated that their maximal EC50 values were generally similar. Studies with antagonists revealed that both 8-(p-sulfophenyl)theophylline (1 microM) and the xanthine amine congener (8-[4-[[[(2-aminoethyl)carbonyl]methyl]oxy]phenyl]1,3- dipropylxanthine (1 microM) inhibited the effects of adenosine (1 nM to 1 microM), but xanthine amine congener was more potent; the latter was markedly effective at 0.1 nM, whereas 8-(p-sulfophenyl)theophylline was nearly ineffective at this concentration. It was also determined that pineal cells generate extracellular adenosine from extracellular ATP. ATP is thought to be released along with catecholamines during neurotransmission. Hence, these studies support the view that adenosine could participate in the transsynaptic regulation of pineal function.

Adenosine↗
PubMed1990

Effects of intrathecal injection of the adenosine receptor agonists R-phenylisopropyl-adenosine and N-ethylcarboxamide-adenosine on nociception and motor function in the rat.

R-phenylisopropyl-adenosine, which has an affinity for the adenosine A1 receptor higher than that for the A2 receptor, and N-ethylcarboxamide-adenosine, which has near equal affinity for the A1 and A2 receptors, were injected intrathecally into rats to evaluate differences in antinociceptive effect and motor impairment. Using the tail-immersion test, both compounds had antinociceptive effects. Motor function was evaluated during spontaneous movement in a free space. N-ethylcarboxamide-adenosine rapidly impaired motor function even after low intrathecal doses. R-phenylisopropyl-adenosine also induced motor impairment, but only after high intrathecal doses, and onset was much slower. These results suggest that the receptor selectivity of R-phenylisopropyl-adenosine is diminished at higher doses and that the motor impairment is an A2-receptor-mediated effect. A selective A1 receptor agonist, e.g., R-phenylisopropyl-adenosine, which produces a good antinociceptive effect without motor impairment, is more promising as a drug of possible use for the future treatment of clinical pain.

Adenosine↗