Activation of adenosine receptors induces c-fos, but not c-jun, expression in neuron-glia hybrids and fibroblasts.
Extracellular adenosine acts through specific cell surface receptors to modulate numerous physiological processes in both the CNS and peripheral tissues (e.g. neurotransmitter release and blood flow). Activation of A1 or A2 adenosine receptors leads to decreased or increased intracellular cAMP levels, respectively. Fos and Jun are nuclear proto-oncogene products, which, like cAMP, appear to act as intermediates in a number of signal transduction pathways. Since increases in both adenosine release and Fos and Jun expression occur in the brain following seizures, we wanted to determine whether Fos and Jun induction might occur as a result of adenosine receptor activation. 3T3 fibroblasts and NG108-15 neuroblastoma-glioma hybrid cells were chosen for study, since they were known to respond to adenosine agonists with changes in cAMP levels. The membranes of NG108-15 cells were shown to have A2-like binding activity in a competitive binding assay. Cultures of each cell line were treated with the adenosine agonists, CHA (A1-selective) and NECA (non-selective adenosine agonist). Both lines responded with a concentration-dependent transient increase in c-fos, but not c-jun, mRNA content after treatment with either agonist. The kinetics of the response were much more rapid for 3T3 cells (peak between 15 and 30 min) than for NG cells (peak between 60 and 90 min). The slower, more prolonged response in the NG108-15 cells is more similar to the time interval between adenosine release and the peak of c-fos mRNA induction in brains of animals following the administration of seizure-promoting drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
Gubits
R M
RM
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Wollack
J B
JB
Yu
H
H
Liu
W K
WK
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006822:Hybrid Cells; D007150:Immunohistochemistry; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011983:Receptors, Purinergic / Q000187:drug effects*
D012333:RNA, Messenger; D011983:Receptors, Purinergic