CL 218,872 binding to benzodiazepine receptors in rat spinal cord: modulation by gamma-aminobutyric acid and evidence for receptor heterogeneity

J Neurochem. 1984 Oct;43(4):903-5. doi: 10.1111/j.1471-4159.1984.tb12823.x.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzodiazepinones / metabolism
  • Cerebral Cortex / metabolism
  • Flumazenil
  • Male
  • Muscimol / pharmacology
  • Pyridazines / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / metabolism*
  • Receptors, GABA-A
  • Spinal Cord / metabolism*
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • Benzodiazepinones
  • Pyridazines
  • Receptors, Cell Surface
  • Receptors, GABA-A
  • Muscimol
  • Flumazenil
  • gamma-Aminobutyric Acid
  • CL 218872