Benzodiazepines modulate the A2 adenosine binding sites on 108CC15 neuroblastoma × glioma hybrid cells

Abstract

We have demonstrated high affinity diazepam binding sites of the Ro5–4864 benzodiazepine receptor subtype on 108CC15 neuroblastoma × 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 (cylic 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. 1984 British Pharmacological Society