A(2A) adenosine receptors inhibit ATP-induced Ca2+ influx in PC12 cells by involving protein kinase A

Abstract

The regulatory role of A(2A) 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 A(2A) 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 A(2A) adenosine receptors leads to inhibition of P2 purinoceptor-mediated Ca2+ influx through ATP-gated cation channels and involves protein kinase A.