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J Biol Chem, Vol. 273, Issue 8, 4718-4724, February 20, 1998
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From the Departments of The antagonistic interactions between adenosine
A1 and dopamine D1 receptors were studied
in a mouse Ltk Neuroscience,
¶ Physiology and Pharmacology, and ** Molecular Biochemistry and
Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden and the
Department of Pharmacology, University of California,
Irvine, California 92697-4625
cell line stably cotransfected with human
adenosine A1 receptor and dopamine D1 receptor
cDNAs. In membrane preparations, both the adenosine A1
receptor agonist N6-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.
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