Combined treatment with hyaluronan inhibitor Pep-1 and a selective adenosine A2 receptor agonist reduces inflammation in experimental arthritis

The effects of adenosine in the nonischemic heart have been shown to be mediated via its binding to extracellular adenosine A1 and A2 receptors located predominantly on myocytes and endothelial cells, respectively. We tested the hypothesis that the beneficial effect of adenosine on postischemic myocardial function is mediated via an adenosine A1 receptor mechanism. Isolated rat hearts perfused at constant pressure (85 cmH2O) were subjected to 30 min of global no-flow ischemia (37 degrees C) and 45 min of reperfusion. Hearts treated with adenosine (100 microM) and the adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA; 0.25 microM) recovered 72 +/- 4 and 70 +/- 4% of preischemic left ventricular developed pressures (LVDP), respectively, after 45 min of reperfusion compared with untreated hearts (54 +/- 3% of preischemic LVDP). Adenosine and CHA hearts exhibited greater myocardial ATP contents than control hearts after 10 min of ischemia, but there were no differences in tissue ATP levels after 30 min of ischemia. In contrast, hearts treated with the adenosine A2 receptor agonist phenylaminoadenosine (0.25 microM) failed to demonstrate improved postischemic function (52 +/- 5%). The addition of the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked the cardioprotective effect of adenosine (57 +/- 4%). These results suggest that adenosine enhances postischemic myocardial function via an A1 receptor mechanism.

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Vasodepressor mechanisms of 2-(1-octynyl)-adenosine (YT-146), a selective adenosine A2 receptor agonist, involve the opening of glibenclamide-sensitive K+ channels

European Journal of Pharmacology ◽

10.1016/0014-2999(92)90682-t ◽

1992 ◽

Vol 213 (2) ◽

pp. 199-204 ◽

Cited By ~ 23

Author(s):

Fumiya Yoneyama ◽

Hiroaki Yamada ◽

Keisuke Satoh ◽

Norio Taira

Keyword(s):

Receptor Agonist ◽

K Channels ◽

Adenosine A2 Receptor

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IB-MECA, an Adenosine A3 Receptor Agonist, Does Not Influence Survival of Lethally γ-Irradiated Mice

Physiological Research ◽

10.33549/physiolres.932411 ◽

2012 ◽

pp. 649-654

Author(s):

M. HOFER ◽

M. POSPÍŠIL ◽

L. DUŠEK ◽

Z. HOFEROVÁ ◽

D. KOMŮRKOVÁ

Keyword(s):

Receptor Agonist ◽

Combined Treatment ◽

Radiation Doses ◽

Moderate Increase ◽

Adenosine A3 Receptor ◽

Post Irradiation ◽

Administration Routes ◽

Treatment Regimens ◽

Drug Doses ◽

Adenosine A3 Receptor Agonist

In our previous studies, IB-MECA, an adenosine A3 receptor agonist, was found to stimulate proliferation of hematopoietic progenitor and precursor cells in mice. This property of IB-MECA was considered to be responsible for its ability to support regeneration of suppressed hematopoiesis after irradiation with sublethal doses of γ-rays when the drug was given in a post-irradiation treatment regimen. This study was aimed at assessing the ability of IB-MECA to influence a 30-day survival of lethally irradiated mice. In a series of experiments, IB-MECA was administered following various lethal radiation doses in various numbers of drug doses and various administration routes. Though in some of these experiments a moderate increase in 30-day survival was observed in IB-MECA-treated mice, the differences in comparison with the controls were not significantly different. It can be inferred from these results and those of previous studies assessing the effects of IB-MECA after sublethal radiation doses that IB-MECA can probably influence only a substantially preserved hematopoiesis like that remaining after sublethal irradiation. Future studies should be aimed at evaluation of the abilities of IB-MECA to influence post-irradiation survival when administered as a part of combined treatment regimens.

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