Up-regulation of A(2A) adenosine receptors by proinflammatory cytokines in rat PC12 cells.
The purpose of this study was to examine the regulation of A(2A) adenosine receptor (A(2A) AR) gene expression induced by proinflammatory cytokines in PC12 cells. The A(2A) AR mRNA levels were substantially increased following 3-48 hr PC12 cell treatment with interleukin 1 beta (500 unit/mL) or tumor necrosis factor alpha (1000 unit/mL), as revealed by RT-PCR analysis. In parallel, cell cytokine treatment induced an up-regulation of A(2A) receptor protein. Equilibrium radioligand binding studies on treated-cells showed a significant increase in maximum density of [3H] 2-(carboxyethylphenylethylamino) adenosine-5'-carboxamide binding sites, with no significant changes in the affinity constant value. The increase in A(2A) receptor density was also demonstrated by Western blot analysis. Interleukin 1 beta and tumor necrosis factor alpha effects on A(2A) AR mRNA and protein levels were detectable after 3 hr cytokine treatment and reached a maximum within 24 and 48 hr, respectively. These results demonstrated the existence of heterologous regulation of A(2A) ARs by proinflammatory cytokines. The biological significance of this regulation might be associated with modulating cellular activity in response to tissue damage associated with inflammatory mediator production.
Trincavelli
Maria L
ML
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, Via Bonanno 6, Italy.
Costa
Barbara
B
Tuscano
Daniela
D
Lucacchini
Antonio
A
Martini
Claudia
C
D000818:Animals; D016207:Cytokines / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014409:Tumor Necrosis Factor-alpha