CL 218,872 Binding to Benzodiazepine Receptors in Rat Spinal Cord: Modulation by γ-Aminobutyric Acid and Evidence for Receptor Heterogeneity |
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Authors: | John W Villiger |
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Institution: | Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, Auckland, New Zealand |
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Abstract: | 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. |
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Keywords: | [3H]Ro 15–1788 Triazolopyridazine Spinal cord Benzodiazepine receptor γ-Aminobutyric acid |
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