title: Effects of YT-146 [2-(1-octynyl) adenosine], an adenosine A2A 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 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.
authors.affiliation: Department of Pharmacology, Fukushima Medical College, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ono
authors.forename: I
authors.initials: I
authors.lastname: Matsuoka
authors.forename: S
authors.initials: S
authors.lastname: Ohkubo
authors.forename: J
authors.initials: J
authors.lastname: Kimura
authors.forename: H
authors.initials: H
authors.lastname: Nakanishi
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000480:Alkynes / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D016716:PC12 Cells; D011189:Potassium Chloride / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D043705:Receptor, Adenosine A2A; D013449:Sulfonamides; D013873:Thionucleotides / Q000494:pharmacology; D014316:Tritium; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000480:Alkynes; D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D007476:Ionophores; D007546:Isoquinolines; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D013449:Sulfonamides; D013873:Thionucleotides; D014665:Vasodilator Agents; D014316:Tritium; D005576:Colforsin; C016957:adenosine-3',5'-cyclic phosphorothioate; D000001:Calcimycin; D003994:Bucladesine; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D002217:Carbachol; C070494:YT 146; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000241:Adenosine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium; D009638:Norepinephrine