VOLATILE ANESTHETICS BIDIRECTIONALLY AND STEREOSPECIFICALLY MODULATE LIGAND-BINDING TO GABA RECEPTORS

Pharmacologically relevant concentrations of volatile anesthetics can bidirectionally modulate radioligand binding to GABA(A) receptors. In mouse cerebral cortex, halothane (a prototypic volatile anesthetic) increased [H-3]muscimol (a GABA receptor agonist) binding while inhibiting the binding of a GABA receptor antagonist ([H-3]SR 95531). These bidirectional effects of inhalational anesthetics on ligand binding to GABA receptors are effected through changes in the B-max with no significant alterations in the K-D of these radioligands. Moreover, the concentration dependent, bidirectional modulation of radioligand binding to GABA receptors by volatile anesthetics exhibited stereoselectivity. Thus, (+)-isoflurane was about twice as potent as the (-)-enantiomer in enhancing [H-3]muscimol binding and similar to 50% more potent as an inhibitor of [H-3]SR 95531 binding, respectively. The demonstration of a bidirectional, stereospecific modulation of radioligand binding to GABA receptors by inhalational agents is consistent with the presence of specific recognition sites for inhalational anesthetics on the GABA(A) receptor complex.