Bd. Harris et al., VOLATILE ANESTHETICS BIDIRECTIONALLY AND STEREOSPECIFICALLY MODULATE LIGAND-BINDING TO GABA RECEPTORS, European journal of pharmacology. Molecular pharmacology section, 267(3), 1994, pp. 269-274
Pharmacologically relevant concentrations of volatile anesthetics can
bidirectionally modulate radioligand binding to GABA(A) receptors. In
mouse cerebral cortex, halothane (a prototypic volatile anesthetic) in
creased [H-3]muscimol (a GABA receptor agonist) binding while inhibiti
ng the binding of a GABA receptor antagonist ([H-3]SR 95531). These bi
directional effects of inhalational anesthetics on ligand binding to G
ABA receptors are effected through changes in the B-max with no signif
icant alterations in the K-D of these radioligands. Moreover, the conc
entration dependent, bidirectional modulation of radioligand binding t
o GABA receptors by volatile anesthetics exhibited stereoselectivity.
Thus, (+)-isoflurane was about twice as potent as the (-)-enantiomer i
n enhancing [H-3]muscimol binding and similar to 50% more potent as an
inhibitor of [H-3]SR 95531 binding, respectively. The demonstration o
f 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 GAB
A(A) receptor complex.