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ANESTHETIC PHARMACOLOGY

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

Waggoner Center for Alcohol and Addiction Research and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas

Address correspondence and reprint requests to R. Adron Harris, PhD, Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, 2500 Speedway MBB 1.124, Austin, TX 78712-1095. Address e-mail to harris{at}mail.utexas.edu

Urethane is widely used as an anesthetic for animal studies because of its minimal effects on cardiovascular and respiratory systems and maintenance of spinal reflexes. Despite its usefulness in animal research, there are no reports concerning its molecular actions. We designed this study to determine whether urethane affects neurotransmitter-gated ion channels. We examined the effects of urethane on recombinant -aminobutyric acid_A, glycine, N-methyl-D-aspartate, -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, -aminobutyric acid_A, and glycine receptors, and it inhibited N-methyl-D-aspartate and -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.

IMPLICATIONS: Urethane modestly affects multiple neurotransmitter systems at an anesthetic concentration. Our findings suggest that these degenerate effects of urethane can produce anesthesia and that urethane has a potential to influence neuronal measurements made in in vivo preparations.

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