Adenosine A2A receptors are colocalized with and activate Golf in rat striatum
Adenosine A2A receptors are colocalized with and activate Golf in rat striatum
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DOI：
10.1124/mol.58.4.771
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发表时间：
2000-10-01
影响因子：
3.6
通讯作者：
Fredholm, BB
中科院分区：
文献类型：
--
作者：
Kull, B;Svenningsson, P;Fredholm, BB
cRNA探针原位杂交显示，A（2A）受体和G（olf）mRNA在尾壳核、丘脑核和嗅结节中大量表达，而G（s）mRNA在A（2A）受体表达区表达较低。在尾壳核中，49%的中型神经元样细胞显示腺苷A（2A）受体mRNA的强信号，98%的中型神经元样细胞显示G（olf）mRNA的强信号。相比之下，G（s）mRNA仅见于尾壳核中12%的中型神经元样细胞。应用原位杂交技术研究腺苷A（2A）受体mRNA与G（olf）或G（s）mRNA的共表达。在尾壳核中，大多数（91-95%）含有腺苷A（2A）受体mRNA的神经元也表达G（olf）mRNA，而只有3 - 5%的含有腺苷A（2A）受体mRNA的神经元同时表达G（s）mRNA。A（2A）受体激动剂CGS 21680 [2-[p-（2-羰基乙基）苯乙基氨基-5 '-N-乙基羧酰胺腺苷]剂量依赖性地激活纹状体膜中的Golf亚基，如用[α-P-32] m-乙酰苯胺基-GTP光标记，然后用抗G（olf）的特异性抗体免疫沉淀所示。将G（olf）cDNA转染到稳定表达人腺苷A（2A）受体的中国仓鼠卵巢细胞中，导致CGS 21680的功效增加，如通过更强的cAMP反应所证明的，表明A（2A）受体激活G（olf）导致生物信号。总之，这些结果提供了解剖学和生物化学证据，腺苷A（2A）受体刺激G（olf），而不是G（s）在纹状体。
In situ hybridization with cRNA probes showed A(2A) receptor and G(olf) mRNAs to be abundantly expressed in caudate putamen, nucleus accumbens, and olfactory tubercle, whereas G(s) mRNA shows a comparatively low expression in regions expressing A(2A) receptors. In caudate putamen, 49% of the medium-sized neuron-like cells exhibited a strong signal for adenosine A(2A) receptor mRNA, and 98% showed a strong signal for G(olf) mRNA. In contrast, G(s) mRNA was found in only 12% of the medium-sized neuron-like cells in caudate putamen. The coexpression of adenosine A(2A) receptor mRNA with that of G(olf) or G(s) mRNAs was studied with double in situ hybridization. A large majority (91-95%) of the neurons in caudate-putamen that contained adenosine A(2A) receptor mRNA also expressed G(olf) mRNA, whereas only 3 to 5% of the neurons with adenosine A(2A) receptor mRNA coexpressed G(s) mRNA. The A(2A) receptor agonist CGS 21680 [2-[p-(2-carbonylethyl) phenylethylamino-5'-N-ethylcarboxamidoadenosine] dose dependently activated Golf subunits in striatal membranes as shown by photolabeling with [ alpha-P-32]m-acetylanilido-GTP followed by immunoprecipitation with a specific antibody against G(olf). Transfection of G(olf) cDNA into Chinese hamster ovary cells, which stably express human adenosine A(2A) receptors, led to an increased efficacy of CGS 21680, as evidenced by a stronger cAMP response, indicating that activation of G(olf) by A(2A) receptors leads to a biological signal. In conclusion, these results provide anatomical and biochemical evidence that adenosine A(2A) receptors stimulate G(olf) rather than G(s) in striatum.