Adenosine A1 Receptor-mediated Modulation of Dopamine D1 Receptors in Stably Cotransfected Fibroblast Cells

The antagonistic interactions between adenosine A 1 and dopamine D 1 receptors were studied in a mouse Ltk − cell line stably cotransfected with human adenosine A 1 receptor and dopamine D 1 receptor cDNAs. In membrane preparations, both the adenosine A 1 receptor agonist N 6 -cyclopentyladenosine and the GTP analogue guanyl-5′-yl imidodiphospate induced a decrease in the proportion of dopamine D 1 receptors in a high affinity state. In the cotransfected cells, the adenosine A 1 agonist induced a concentration-dependent inhibition of dopamine-induced cAMP accumulation. Blockade of adenosine A 1 receptor signal transduction with the adenosine A 1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine or with pertussis toxin pretreatment increased both basal and dopamine-stimulated cAMP levels, indicating the existence of tonic adenosine A 1 receptor activation. Pretreatment with pertussis toxin also counteracted the effects of low concentrations of the A 1 agonist on D 1 receptor-agonist binding. The results suggest that adenosine A 1 receptors antagonistically modulate dopamine D 1 receptors at the level of receptor binding and the generation of second messengers.