Adenosine A sub(1) receptor-mediated modulation of dopamine D sub(1) receptors in stably cotransfected fibroblast cells

The antagonistic interactions between adenosine A sub(1) and dopamine D sub(1) receptors were studied in a mouse Ltk super(-) cell line stably cotransfected with human adenosine A sub(1) receptor and dopamine D sub(1) receptor cDNAs. In membrane preparations, both the adenosine A sub(1) receptor agonist N super(6)-cyclopentyladenosine and the GTP analogue guanyl-5'y1 imidodiphospate induced a decrease in the proportion of dopamine D sub(1) receptors in a high affinity state. In the cotransfected cells, the adenosine A sub(1) agonist induced a concentration-dependent inhibition of dopamine-induced cAMP accumulation. Blockade of adenosine A sub(1) receptor signal transduction with the adenosine A sub(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 sub(1) receptor activation. Pretreatment with pertussis toxin also counteracted the effects of low concentrations of the A sub(1) agonist on D sub(1) receptor-agonist binding. The results suggest that adenosine A sub(1) receptors antagonistically modulate dopamine D sub(1) receptors at the level of receptor binding and the generation of second messengers.