Adenosine A_2A receptors modulate the binding characteristics of dopamine D₂ receptors in stably cotransfected fibroblast cells

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• 作者：Dasgupta ; Sarmila ; Ferré ; Sergi ; Kull ; Bjö ; rn ; Hedlund ; Peter B. ; Finnman ; Ulla-Britt ; et. al.
• 关键词：Adenosine ; Dopamine ; Adenylyl cyclase ; Fibroblast ; Receptor-receptor interaction
• 刊名：European Journal of Pharmacology
• 出版年：1996
• 出版时间：December 5, 1996
• 年：1996
• 卷：316
• 期：2-3
• 页码：325-331
• 全文大小：706 K

文摘

In membrane preparations from rat striatum, where adenosine A_2A and dopamine D₂ receptors are coexpressed, stimulation of adenosine A_2A receptors was found to decrease the affinity of dopamine D₂ receptors for dopamine agonists. We now demonstrate the existence of this antagonistic interaction in a fibroblast cell line (Ltk⁻) stably transfected with the human dopamine D₂ (long-form) receptor and the dog adenosine A_2A receptor cDNAs (A_2A-D₂ cells). In A_2A-D₂ cells, but not in control cells only containing dopamine D₂ receptors (D₂ cells), the selective adenosine A_2A agonist 2-[p-(2-carboxyethyl)-phenethylamino]-5′-N-ethyl-carboxamido adenosine (CGS 21680) induced a 2-3-fold decrease in the affinity of dopamine D₂ receptors for dopamine, as shown in competition experiments with dopamine versus the selective dopamine D₂ antagonist [³H]raclopride. By contrast, activation of the constitutively expressed adenosine A_2B receptors with 5′-N-ethyl-carboxamidoadenosine (NECA) did not modify dopamine D₂ receptor binding. In A_2A-D₂ cells CGS 21680 failed to induce or induced only a small increase in adenosine-3′,5′-cyclic-monophosphate (cAMP) accumulation. In D₂ cells NECA- or forskolin-induced adenylyl cyclase activation was not associated with any change in dopamine D₂ receptor binding. These results indicate that adenylyl cyclase activation is not involved in the adenosine A_2A receptor-mediated modulation of the binding characteristics of the dopamine D₂ (long-form) receptor.