Peterfreund R A, Gies E K, Fink J S
Massachusetts General Hospital, Department of Anesthesia and Critical Care, Harvard Medical School, Boston 02114, USA.
Eur J Pharmacol. 1997 Oct 1;336(1):71-80. doi: 10.1016/s0014-2999(97)01194-1.
Protein kinase C regulates mRNAs encoding several G protein-linked receptors but its role in adenosine A2a receptor expression is not known. We tested the hypothesis that protein kinase C activated by tetradecanoyl phorbol acetate (TPA) regulates adenosine A2a receptor mRNA levels. SH-SY5Y human neuroblastoma cells express adenosine receptors which positively couple to adenylyl cyclase with a pharmacologic profile expected of the A2a subtype. Northern blotting demonstrated an adenosine A2a receptor mRNA species of similar molecular size in SH-SY5Y cells and in human brain. TPA increased adenosine A2a receptor mRNA in a dose- and time-dependent fashion. Transcription or translation inhibition prevented increases in adenosine A2a receptor mRNA. Bisindolylmaleimide blocked TPA effects. Adenosine A2a receptor mRNA stability was unchanged by TPA. This study identifies a human neuroblastoma cell line expressing functional adenosine A2a receptors. Protein kinase C activation appears to enhance transcription of the adenosine A2a receptor gene.
蛋白激酶C调节几种G蛋白偶联受体的编码mRNA，但它在腺苷A2a受体表达中的作用尚不清楚。我们检验了一个假说，即由十四酰佛波醇乙酸酯（TPA）激活的蛋白激酶C调节腺苷A2a受体mRNA水平。SH-SY5Y人神经母细胞瘤细胞表达腺苷受体，这些受体与腺苷酸环化酶呈正偶联，具有A2a亚型预期的药理学特征。Northern印迹法显示，SH-SY5Y细胞和人脑中有分子大小相似的腺苷A2a受体mRNA种类。TPA以剂量和时间依赖性方式增加腺苷A2a受体mRNA。转录或翻译抑制可阻止腺苷A2a受体mRNA的增加。双吲哚马来酰胺阻断TPA的作用。TPA对腺苷A2a受体mRNA稳定性无影响。本研究鉴定出一种表达功能性腺苷A2a受体的人神经母细胞瘤细胞系。蛋白激酶C激活似乎增强了腺苷A2a受体基因的转录。
