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 hue 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 cotransfect-ed 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.