Effects of propentofylline on adenosine receptor activity in Chinese hamster ovary cell lines transfected with human A1, A2A, or A2B receptors and a luciferase reporter gene

Propentofylline is neuroprotective in vivo; but its mechanism of action is not completely understood. Previously, propentofylline was shown to black: adenosine transport processes, to inhibit three adenosine receptor subtypes, and to inhibit cAMP phosphodiesterase. We tested the effect of propentofylline on adenosine receptor function in Chinese hamster ovary (CHO) cells transfected with human adenosine A(1), A(2A), or A(2B) receptors and a luciferase reporter gene under control of a promoter sequence containing several copies of the cAMP response element. We investigated the concentration-dependent inhibitory effects of propentofylline on cAMP phosphodiesterase, adenosine transport processes, and adenosine A(1), A(2A), and A(2B) receptors. At concentrations greater than or equal to 1 mM, propentofylline increased luciferase activity probably as a result of inhibition of cAMP phosphodiesterase. Inhibition of [H-3]adenosine uptake by propentofylline was concentration dependent, with IC50 values of 37-39 mu M for the three cell types. Agonist-activated adenosine A(1) receptors were antagonized by 100 mu M propentofylline, but inhibition of agonist-stimulated A(2A) or A(2B) receptors was not observed. In contrast, A(1) and A(2A) receptor mediated effects of adenosine were enhanced by propentofylline at concentrations of 1 and 100 mu M, respectively. These data indicate that the net effects of propentofylline in vivo will be dependent on the concentrations of propentofylline and adenosine available and on the subtypes of adenosine receptors, phosphodiesterases, and nucleoside transporters present.