RRC ID 39254
Author Ono T, Matsuoka I, Ohkubo S, Kimura J, Nakanishi H.
Title Effects of YT-146 [2-(1-octynyl) adenosine], an adenosine A2A receptor agonist, on cAMP production and noradrenaline release in PC12 cells.
Journal Jpn J Pharmacol
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 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.
Volume 78(3)
Pages 269-77
Published 1998-11-1
DOI 10.1254/jjp.78.269
PMID 9869260
MeSH Adenosine / analogs & derivatives* Adenosine / pharmacology Adenosine Triphosphate / pharmacology Alkynes / pharmacology* Animals Bucladesine / pharmacology Calcimycin / pharmacology Calcium / metabolism Carbachol / pharmacology Cholinergic Agonists / pharmacology Colforsin / pharmacology Cyclic AMP / analogs & derivatives Cyclic AMP / biosynthesis* Cyclic AMP / pharmacology Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors Enzyme Inhibitors / pharmacology Ionophores / pharmacology Isoquinolines / pharmacology Membrane Potentials / drug effects Norepinephrine / metabolism* PC12 Cells Potassium Chloride / pharmacology Purinergic P1 Receptor Agonists* Rats Receptor, Adenosine A2A Sulfonamides* Thionucleotides / pharmacology Tritium Vasodilator Agents / pharmacology*
Times Cited 6
Human and Animal Cells PC-12(RCB0009)