Protein kinase C regulates adenosine A2a receptor mRNA expression in SH-SY5Y cells.
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.
Peterfreund
R A
RA
Massachusetts General Hospital, Department of Anesthesia and Critical Care, Harvard Medical School, Boston 02114, USA. peterfreund@etherdome.mgh.harvard.edu
Gies
E K
EK
Fink
J S
JS
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009447:Neuroblastoma; D010627:Phenethylamines / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D010627:Phenethylamines; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000242:Cyclic AMP; D011493:Protein Kinase C; D000241:Adenosine; D013755:Tetradecanoylphorbol Acetate