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Published on: January 27, 2014
Adenosine A1 receptor-mediated modulation of dopamine D1 receptors in stably cotransfected fibroblast cells
S Ferré1, M Torvinen, K Antoniou
1Department of Neuroscience, Karolinska Institute, S-171 77 Stockholm, Sweden.
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 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.
Insights
Adenosine A1 receptors inhibit dopamine D1 receptors, affecting their binding and signaling. This interaction was observed in cell lines, revealing a key mechanism in receptor modulation.
Area of Science:
- Neuroscience
- Molecular Pharmacology
Background:
- Adenosine A1 receptors and dopamine D1 receptors are crucial G protein-coupled receptors involved in various physiological processes.
- Understanding the interplay between these receptors is vital for deciphering complex signaling pathways in the central nervous system.
Purpose of the Study:
- To investigate the antagonistic interactions between adenosine A1 receptors and dopamine D1 receptors.
- To elucidate the mechanisms underlying this modulation at the receptor binding and signaling levels.
Main Methods:
- Utilized a mouse Ltk- cell line stably co-transfected with human adenosine A1 and dopamine D1 receptors.
- Employed receptor binding assays and cAMP accumulation assays to study receptor interactions.
- Investigated the effects of adenosine A1 receptor agonists and antagonists, as well as pertussis toxin.
Main Results:
- Adenosine A1 receptor activation decreased the proportion of high-affinity dopamine D1 receptors.
- Adenosine A1 receptor agonists inhibited dopamine-induced cAMP accumulation in a concentration-dependent manner.
- Blockade of adenosine A1 receptor signaling increased basal and dopamine-stimulated cAMP levels, indicating tonic A1 receptor activation.
Conclusions:
- Adenosine A1 receptors antagonistically modulate dopamine D1 receptors.
- This modulation occurs at both the level of receptor binding affinity and second messenger generation (cAMP).
- Findings suggest a significant cross-talk between adenosine and dopamine signaling pathways.
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