101. Adenosine A1 Receptor-mediated Modulation of Dopamine D1 Receptors in Stably Cotransfected Fibroblast Cells
- Author
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Maria Torvinen, Sergi Ferré, Ernest Arenas, Bertil B. Fredholm, Eva Irenius, Kjell Fuxe, Katerina Antoniou, and Olivier Civelli
- Subjects
DNA, Complementary ,Dopamine ,Pharmacology ,Transfection ,Tritium ,Binding, Competitive ,Biochemistry ,Cell Line ,Mice ,Adenosine A1 receptor ,Dopamine receptor D2 ,Cyclic AMP ,medicine ,Animals ,Humans ,Molecular Biology ,Chemistry ,Receptors, Dopamine D1 ,Receptors, Purinergic P1 ,Cell Biology ,Benzazepines ,Purinergic signalling ,Blotting, Northern ,Adenosine A3 receptor ,Adenosine ,Adenosine receptor ,Purinergic P1 Receptor Antagonists ,Xanthines ,Dopamine Antagonists ,Endogenous agonist ,Adenosine A2B receptor ,Signal Transduction ,medicine.drug - Abstract
The antagonistic interactions between adenosine A1 and dopamine D1 receptors were studied in a mouse Ltk− cell line stably cotransfected with human adenosine A1 receptor and dopamine D1 receptor cDNAs. In membrane preparations, both the adenosine A1receptor agonist N 6-cyclopentyladenosine and the GTP analogue guanyl-5′-yl imidodiphospate induced a decrease in the proportion of dopamine D1 receptors in a high affinity state. In the cotransfected cells, the adenosine A1 agonist induced a concentration-dependent inhibition of dopamine-induced cAMP accumulation. Blockade of adenosine A1 receptor signal transduction with the adenosine A1 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 A1 receptor activation. Pretreatment with pertussis toxin also counteracted the effects of low concentrations of the A1 agonist on D1 receptor-agonist binding. The results suggest that adenosine A1 receptors antagonistically modulate dopamine D1 receptors at the level of receptor binding and the generation of second messengers.
- Published
- 1998