The A1 adenosine receptor antagonist 1,3, dipropyl-8-cyclopentylxanthine (DPCPX) displays adenosine agonist properties in the FRTL5 thyroid cell line

We have evaluated whether the type I adenosine receptor mediates adenosine's ability to inhibit thyrotropin-stimulated cyclic AMP generation and DNA synthesis in FRTL5 cells. The xanthine derivative 1,3-dipropyl-8-cyclopentylxanthine, a selective antagonist for the type 1 adenosine receptor, binds to FRTL5 with high affinity and specificity. 1,3-Dipropyl-8-cyclopentylxanthine does not alter basal cyclic AMP levels but does reverse adenosine's ability to inhibit thyrotropin-stimulated cyclic AMP generation. 1,3-Dipropyl-8-cyclopentylxanthine also potently inhibits thyrotropin-stimulated and dibutyryl cyclic AMP-stimulated 3H]-thymidine incorporation into DNA in FRTL5 cells. Thus, in FRTL5 cells, 1,3-dipropyl-8-cyclopentylxanthine displays both adenosine antagonist and adenosine agonist properties, the latter occurring at a site distal to cyclic AMP generation.