A2A adenosine receptors inhibit ATP-induced Ca2+ influx in PC12 cells by involving protein kinase A.
The regulatory role of A2A adenosine receptors in P2 purinoceptor-mediated calcium signaling was investigated in rat pheochromocytoma (PC12) cells. When PC12 cells were treated with 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680), a specific agonist of the A2A adenosine receptor, the extracellular ATP-evoked rise in cytosolic free Ca2+ concentration ([Ca2+]i) was inhibited by 20%. Both intracellular calcium release and inositol 1,4,5-trisphosphate production evoked by ATP were not affected by CGS-21680 treatment. However, ATP-evoked Ca2+ influx was inhibited following CGS-21680 stimulation. The CGS-21680-mediated inhibition occurred independently of nifedipine-induced inhibition of the [Ca2+]i rise. The CGS-21680-induced inhibition was completely blocked by reactive blue 2. The CGS-21680 effect was mimicked by forskolin and dibutyryl-cyclic AMP and blocked by Rp-adenosine 3',5'-cyclic monophosphothioate, a protein kinase A inhibitor, or by staurosporine, a general kinase inhibitor. The data suggest that in PC12 cells activation of A2A adenosine receptors leads to inhibition of P2 purinoceptor-mediated Ca2+ influx through ATP-gated cation channels and involves protein kinase A.
Park
T J
TJ
Department of Life Science, Pohang University of Science and Technology, Hyoja Dong, Korea.
Song
S K
SK
Kim
K T
KT
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002412:Cations / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004594:Electrophysiology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007425:Intracellular Membranes / Q000378:metabolism; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism; D009994:Osmolar Concentration; D016716:PC12 Cells; D010627:Phenethylamines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D058913:Purinergic Agonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D015220:Calcium Channels; D002412:Cations; D007473:Ion Channels; D010627:Phenethylamines; D058913:Purinergic Agonists; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000241:Adenosine; D002118:Calcium