The Anesthetic Mechanism of Urethane: The Effects on Neurotransmitter-Gated Ion Channels

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Abstract
Rmine whether urethane affects neurotransmitter-gated ion channels. We examined the effects of urethane on recombinant γ-aminobutyric acidA, glycine, N-methyl-d-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, and neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes. Urethane potentiated the functions of neuronal nicotinic acetylcholine, γ-aminobutyric acidA, and glycine receptors, and it inhibited N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors in a concentration-dependent manner. At concentrations close to anesthetic 50% effective concentration, urethane had modest effects on all channels tested, suggesting the lack of a single predominant target for its action. This may account for its usefulness as a veterinary anesthetic. However, a large concentration of urethane exerts marked effects on all channels. These findings not only give insight into the molecular mechanism of anesthetics but also caution that neurophysiologic measurements from animals anesthetized with urethane may be complicated by the effects of urethane on multiple neurotransmitter systems. Our results also suggest that small changes in multiple receptor systems can produce anesthesia....