Functional interactions between adenosine A2A and dopamine D2 receptors have been demonstrated both at the D2 agonist-binding and second messenger levels. The present studies use a [3H]dopamine-binding assay as a sensitive measure of A2A receptor-mediated modulation of D2 receptors. Co-incubation with an A2A receptor agonist increased the Kd value of high-affinity [3H]dopamine-binding sites of the D2 receptor without changing their Bmax values in a cotransfected cell line. This interaction was shown to be subtype specific, as the A2A receptor agonist did not modulate the affinity of the D1 receptor for [3H]dopamine. The domains of the D2 receptor important for the A2A/D2 receptor interaction were studied with chimeric dopamine D2/D1 receptors. The results showed that the A2A receptor agonist still strongly reduced the affinity of a D2/D1 chimera with the sixth transmembrane (TM) domain and third extracellular loop from the D1 receptor. However, the A2A receptor agonist was not able to modulate a D2/D1 chimeric receptor containing the fifth and sixth TM domains and the third intracellular and extracellular loops from the D1 receptor, indicating that the fifth TM domain and/or the third intracellular loop may be involved in the interaction between A2A and D2 receptors.
Biochemical identification of the dopamine D2 receptor domains interacting with the adenosine A2A receptor / M., Torvinen; L. B., Kozell; K. A., Neve; Agnati, Luigi Francesco; K., Fuxe. - In: JOURNAL OF MOLECULAR NEUROSCIENCE. - ISSN 0895-8696. - STAMPA. - 24:(2004), pp. 173-180. [10.1385/JMN:24:2:173]
Biochemical identification of the dopamine D2 receptor domains interacting with the adenosine A2A receptor
AGNATI, Luigi Francesco;
2004
Abstract
Functional interactions between adenosine A2A and dopamine D2 receptors have been demonstrated both at the D2 agonist-binding and second messenger levels. The present studies use a [3H]dopamine-binding assay as a sensitive measure of A2A receptor-mediated modulation of D2 receptors. Co-incubation with an A2A receptor agonist increased the Kd value of high-affinity [3H]dopamine-binding sites of the D2 receptor without changing their Bmax values in a cotransfected cell line. This interaction was shown to be subtype specific, as the A2A receptor agonist did not modulate the affinity of the D1 receptor for [3H]dopamine. The domains of the D2 receptor important for the A2A/D2 receptor interaction were studied with chimeric dopamine D2/D1 receptors. The results showed that the A2A receptor agonist still strongly reduced the affinity of a D2/D1 chimera with the sixth transmembrane (TM) domain and third extracellular loop from the D1 receptor. However, the A2A receptor agonist was not able to modulate a D2/D1 chimeric receptor containing the fifth and sixth TM domains and the third intracellular and extracellular loops from the D1 receptor, indicating that the fifth TM domain and/or the third intracellular loop may be involved in the interaction between A2A and D2 receptors.Pubblicazioni consigliate
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris