Effects of YT-146 [2-(1-Octynyl) Adenosine], an Adenosine A2A Receptot Agonist, on cAMP Production and Noradrenaline Release in PC12 Cells

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  • Effects of YT-146 (2-(1-Octynyl) Adenosine), an Adenosine A2A Receptor Agonist, on cAMP Production and Noradrenaline Release in PC12 Cells.
  • Effects of YT-146 2 1 Octynyl Adenosine

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Effects of YT-146 [2-(1-octynyl) adenosine], an adenosine A2 receptor agonist, on cAMP production and noradrenaline (NA) release were investigated in PC12 cells. YT-146 caused a concentration-dependent cAMP accumulation (EC50: 1.2±0.9 nM). In [3H]NA-prelabeled cells, YT-146 increased the basal NA release and enhanced ATP-evoked NA release in a concentration-dependent manner (EC50: 0.23±0.15 nM). YT-146 augmented the maximal response to ATP without affecting the EC50 value of ATP. These effects of YT-146 were inhibited by several adenosine receptor antagonists with a characteristic of adenosine A2A receptor subtype. The effects of YT-146 were mimicked by forskolin, dibutylyl cAMP and Sp-cAMPS, and inhibited by H-89, a cAMP-dependent protein kinase inhibitor. YT-146 had little effect on ATP-induced increase in intracellular Ca2+ concentration. YT-146 enhanced the NA release induced by several different stimuli including Ca2+ ionophore A23187. The present results suggest that YT-146 is a potent agonist on adenosine A2A receptors in PC12 cells and causes a cAMP-dependent enhancement of NA release by affecting the exocytosis process at a point downstream of the intracellular Ca2+ increase.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 78 (3), 269-277, 1998

    公益社団法人 日本薬理学会

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