Adenosine A(2A) receptors modulate the binding characteristics of dopamine D-2 receptors in stably cotransfected fibroblast cells
Adenosine A(2A) receptors modulate the binding characteristics of dopamine D-2 receptors in stably cotransfected fibroblast cells
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DOI：
10.1016/s0014-2999(96)00665-6
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发表时间：
1996-12-05
影响因子：
5
通讯作者：
Fuxe, K
中科院分区：
文献类型：
--
作者：
Dasgupta, S;Ferre, S;Fuxe, K
在来自大鼠纹状体的膜制备物中，腺苷A（2A）和多巴胺D-2受体共表达，发现腺苷A（2A）受体的刺激降低多巴胺D-2受体对多巴胺激动剂的亲和力，我们现在证明了在稳定转染人多巴胺D-2的成纤维细胞系（Ltk（-））中存在这种拮抗相互作用（长型）受体和狗腺苷A（2A）受体cDNA（A（2A）-D-2细胞）。在A（2A）-D-2细胞中，而在仅含有多巴胺D-2受体的对照细胞中则没有（D-2细胞），选择性腺苷A（2A）激动剂2-[p-（2-羧乙基）-苯乙氨基]-5 '-N-乙基-甲酰氨基腺苷（CGS 21680）诱导多巴胺D-2受体对多巴胺的亲和力降低2-3倍，如多巴胺与选择性多巴胺D-2拮抗剂[H-3]雷氯必利的竞争实验所示。相比之下，用5 '-N-乙基-甲酰氨基腺苷（NECA）激活组成型表达的腺苷A（2B）受体不会改变多巴胺D-2受体结合。在A（2A）-D-2细胞中，CGS 21680不能诱导或仅诱导了3 '，5'-环磷酸腺苷（cAMP）积累的少量增加。在D-2细胞中，NECA或毛喉素诱导的腺苷酸环化酶激活与多巴胺D-2受体结合的任何变化无关。这些结果表明，腺苷酸环化酶激活不参与腺苷A（2A）受体介导的多巴胺D-2（长型）受体结合特性的调节。
In membrane preparations from rat striatum, where adenosine A(2A) and dopamine D-2 receptors are coexpressed, stimulation of adenosine A(2A) receptors was found to decrease the affinity of dopamine D-2 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 D-2 (long-form) receptor and the dog adenosine A(2A) receptor cDNAs (A(2A)-D-2 cells). In A(2A)-D-2 cells, but not in control cells only containing dopamine D-2 receptors (D-2 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 D-2 receptors for dopamine, as shown in competition experiments with dopamine versus the selective dopamine D-2 antagonist [H-3]raclopride. By contrast, activation of the constitutively expressed adenosine A(2B) receptors with 5'-N-ethyl-carboxamidoadenosine (NECA) did not modify dopamine D-2 receptor binding. In A(2A)-D-2 cells CGS 21680 failed to induce or induced only a small increase in adenosine 3',5'-cyclic-monophosphate (cAMP) accumulation. In D-2 cells NECA- or forskolin-induced adenylyl cyclase activation was not associated with any change in dopamine D-2 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 D-2 (long-form) receptor.