The role of adenosine A 1 receptors in the ATP-evoked Ca 2+ response in rat thyroid FRTL-5 cells

Abstract

The effect of adenosine A 1 receptor activation on the ATP-induced increase in intracellular free Ca 2+ was studied in control and protein kinase C down-regulated Fisher rat thyroid (FRTL-5) cells. Long-term phorbol ester treatment, which leads to protein kinase C down-regulation, enhanced the ATP-evoked extracellular Ca 2+ influx. The increased Ca 2+ influx was antagonized by the adenosine A 1 receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX). [ 3H]DPCPX binding studies revealed that phorbol ester-treatment increased the number of adenosine A 1 receptors. The adenosine A 1 receptor-mediated inhibition of the cyclic AMP formation was not affected by the increased receptor number. We conclude that the enhanced ATP-evoked Ca 2+ influx in protein kinase C down-regulated cells is mediated by adenosine formed by hydrolysis of ATP, and that this adenosine interacts with the increased number of A 1 receptors. The mechanism by which adenosine enhances Ca 2+ entry is not known. Thus, the larger number of adenosine A 1 receptors broadens the spectrum of adenosine A 1 receptor affected signaling systems in FRTL-5 cells.