Effects of YT-146 [2-(1-Octynyl) Adenosine], an Adenosine A_2A Receptor Agonist, on cAMP Production and Noradrenaline Release in PC12 Cells

Abstract

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 A_2A 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 A_2A 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.