Stimulation of P2Y-purinoceptors on astrocytes results in immediate early gene expression and potentiation of neuropeptide action.
The action of adenosine-5'-O-(2-thiodiphosphate), a non-hydrolysable purine analogue and potent P2Y1-purinoceptor agonist, was studied on immediate early gene expression in rat astrocyte cultures. A rapid and transient increase in c-fos, junB, c-jun and Tis11 messenger RNA was observed in cultured astrocytes after treatment with adenosine-5'-O-(2-thiodiphosphate). Maximal induction of immediate early gene expression was obtained within 30 min of stimulation and c-fos was the most sensitive indicator of P2Y-purinoceptor activation. Calcitonin gene-related peptide has also been shown to be a potent inducer of c-fos messenger RNA in cultured astroglial cells. The combined stimulation of astrocytes with calcitonin gene-related peptide and adenosine-5'-O-(2-thiodiphosphate) resulted in the potentiated expression of c-fos messenger RNA. The superinduction of immediate early gene expression by calcitonin gene-related peptide and extracellular ATP in cultured astrocytes might result from intracellular signal transduction cross-talk, since adenosine-5'-O-(2-thiodiphosphate) was found to increase calcitonin gene-related peptide-induced cyclic AMP accumulation by 35%. Phorbol 12-myristate 13-acetate also increased calcitonin gene-related peptide-evoked cyclic AMP accumulation and led to the induction of immediate early gene expression, suggesting that protein kinase C might be at least in part involved in purinergic cross-talk. Our results demonstrate synergistic roles for extracellular ATP and calcitonin gene-related peptide in the transcriptional activation of astroglial cells.
Priller
J
J
Department of Neuromorphology, Max-Planck-Institute of Neurobiology, Martinsried, Germany.
Reddington
M
M
Haas
C A
CA
Kreutzberg
G W
GW
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004268:DNA-Binding Proteins; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D017874:Immediate-Early Proteins; D009479:Neuropeptides / Q000187:drug effects* / Q000494:pharmacology*; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000378:metabolism* / Q000502:physiology; D058472:Receptors, Purinergic P2Y1; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D051816:Tristetraprolin
D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D009479:Neuropeptides; C546384:P2ry1 protein, rat; D011506:Proteins; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides; D051816:Tristetraprolin; C497554:Zfp36 protein, rat; C018444:adenosine 5'-O-(1-thiodiphosphate); D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; D013755:Tetradecanoylphorbol Acetate