Potentiation by adenosine of ATP‐evoked dopamine release via a pertussis toxin‐sensitive mechanism in rat phaeochromocytoma PC12 cells

The effects of adenosine on adenosine 5′‐triphosphate (ATP)‐evoked dopamine release from rat phaeochromocytoma PC12 cells was investigated to determine whether adenosine exerts a regulatory effect on the ATP‐evoked response. Adenosine potentiated ATP (30 μm)‐evoked dopamine release in a concentration‐dependent manner over a concentration‐range of 1 to 100 μm. Adenosine (100 μm) shifted the concentration‐dependence of the ATP‐evoked response to the left without affecting the maximal response. Aminophylline, a non‐selective adenosine receptor antagonist, and CP66713, a selective antagonist at the A₂ subclass of adenosine receptors, abolished the adenosine‐induced potentiation. Furthermore, 8‐cyclopentyltheophylline, a selective antagonist at the adenosine A₁ receptor partially inhibited the adenosine‐evoked potentiation. CGS22492, a selective A₂ receptor agonist, potentiated ATP‐evoked dopamine release whereas N⁶‐cyclohexyladenosine (CHA), a selective A₁ receptor agonist, had no effect. Pertussis toxin (PTX), a bacterial exotoxin which catalyzes the ADP‐ribosylation of guanosine 5′‐triphosphate (GTP)‐binding proteins (G‐proteins), inhibited the adenosine‐induced potentiation of dopamine release. Dibutyryl cyclic AMP (db cyclic AMP), an analogue of cyclic AMP, had no effect on the release on the ATP‐evoked response. Adenosine potentiated the ATP‐evoked rise in intracellular Ca²⁺ concentration ([Ca]_i) in PC12 cells. This potentiation was also observed with CGS 22492 but not with CHA. PTX completely inhibited the adenosine‐induced potentiation of the rise in [Ca]_i. On the basis of these findings, we suggest that the adenosine‐induced potentiation of ATP‐evoked dopamine release was due to an increase in [Ca]_i in the cells. Although the potentiation is most likely mediated by a subclass of A₂ receptors, the subclass may be different from those previously reported since the potentiation was sensitive to PTX and was not reproduced by db cyclic AMP. 1994 British Pharmacological Society