title: Benzodiazepines modulate the A2 adenosine binding sites on 108CC15 neuroblastoma X glioma hybrid cells.
abstract: We have demonstrated high affinity diazepam binding sites of the Ro5-4864 benzodiazepine receptor subtype on 108CC15 neuroblastoma X glioma hybrid cells. These cells were previously shown to have purinoceptors of the A2 adenosine subtype and we have now found that [3H]-adenosine can be displaced from this binding site by the benzodiazepines and related compounds that can also bind to the Ro5-4864 site. Diazepam was found to have no intrinsic activity at the A2-receptor as measured by the stimulation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) production in this cell line. At concentrations sufficient to compete for the A2-receptor, diazepam was shown to facilitate, by approximately 2 fold, the stimulation of cyclic AMP by adenosine. These effects are not due to inhibition of adenosine uptake or phosphodiesterase activity, but are probably a consequence of modulation of the coupling of the A2-receptor to cyclic AMP production in this hybrid cell line.
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D001667:Binding, Competitive / Q000187:drug effects; D002478:Cells, Cultured; D002998:Clonazepam / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D003975:Diazepam / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D006822:Hybrid Cells; D007700:Kinetics; D009447:Neuroblastoma / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D011983:Receptors, Purinergic; D020889:Rolipram
chemical_list: D014151:Anti-Anxiety Agents; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D011983:Receptors, Purinergic; D001569:Benzodiazepines; C014268:ID 690; D002998:Clonazepam; D000242:Cyclic AMP; D020889:Rolipram; D003975:Diazepam