Dissimilarities between benzodiazepine-binding sites and adenosine uptake sites in astrocytes and neurons in primary cultures.
The question whether the benzodiazepine receptor site in astrocytes or in neurons might be identical to the adenosine uptake site was studied by determining pharmacological profiles, inhibition types, and the effects of benzodiazepine antagonists in primary cultures of either astrocytes or neurons. Fourteen different benzodiazepines and five different adenosine uptake inhibitors displaced [3H] diazepam and inhibited adenosine uptake in both astrocytes and neurons. However, the rank orders (determined as IC50 values) with which these two parameters were affected were profoundly different, indicating dissimilarities between these two sites. For several of the compounds a difference in inhibition type (competitive vs. noncompetitive) was observed between the benzodiazepine-binding site and the adenosine uptake site in astrocytes and/or neurons, which further corroborated the conclusion of a difference between the benzodiazepine-binding site and the adenosine uptake site. Finally, the neuronal benzodiazepine antagonists RO 15-1788 and CGS-8216 and the astrocytic benzodiazepine antagonist PK 11195, which reverse the action of benzodiazepines, were not able to reverse inhibition of adenosine uptake by diazepam but exerted an inhibitory effect of their own.
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001569:Benzodiazepines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001665:Binding Sites; D002478:Cells, Cultured; D003975:Diazepam / Q000037:antagonists & inhibitors / Q000378:metabolism; D005442:Flumazenil / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects
D007546:Isoquinolines; D011720:Pyrazoles; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005442:Flumazenil; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D000241:Adenosine; D003975:Diazepam; C037850:PK 11195