ADENOSINE A(1) RECEPTOR-MEDIATED MODULATION OF DOPAMINE D-1 RECEPTORSIN 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, I n 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 h igh affinity state, In the cotransfect-ed cells, the adenosine A(1) ag onist induced a concentration-dependent inhibition of dopamine-induced cAMP accumulation, Blockade of adenosine A(1) receptor signal transdu ction with the adenosine A(1) receptor antagonist 1,3-dipropyl-8-cyclo pentylxanthine or with pertussis toxin pretreatment increased both bas al and dopamine-stimulated cAMP levels, indicating the existence of to nic adenosine A(1) receptor activation, Pretreatment with pertussis to xin also counteracted the effects of low concentrations of the A(1) ag onist on D-1 receptor-agonist binding The results suggest that adenosi ne A(1) receptors antagonistically modulate dopamine D-1 receptors at the level of receptor binding and the generation of second messengers.