CL 218,872 binding to benzodiazepine receptors in rat spinal cord: modulation by gamma-aminobutyric acid and evidence for receptor heterogeneity.
The binding of the triazolopyridazine CL 218,872 to central benzodiazepine receptors identified with [3H]Ro 15-1788 was studied in extensively washed homogenates of rat spinal cord and cerebral cortex. CL 218,872 displacement curves were shallow in both spinal cord (nH = 0.67) and cortex (nH = 0.54), suggesting the presence of type 1 and type 2 benzodiazepine receptors in both tissues. CL 218,872 had lower affinity in spinal cord (IC50 = 825 nM) than cortex (IC50 = 152 nM), possibly reflecting the presence of fewer type 1 sites in the cord. Activating gamma-aminobutyric acid (GABA) receptors with 10 microM muscimol resulted in a two- to threefold increase in CL 218,872 affinity in both tissues without changes in the displacement curve slope. This indicates that GABA enhances CL 218,872 affinity for both type 1 and type 2 sites in both spinal cord and cerebral cortex.
D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005442:Flumazenil; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011724:Pyridazines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A; D013116:Spinal Cord / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001570:Benzodiazepinones; D011724:Pyridazines; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D009118:Muscimol; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C021604:CL 218872