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GENERAL ARTICLES

The Anesthetic Potency of Propanol and Butanol Versus Propanethiol and Butanethiol in 1 Wild Type and 1(S267Q) Glycine Receptors

Maria Paola Mascia, PhD^*, Diane H. Gong, BS, Edmond I Eger, II, MD, and R. Adron Harris, PhD^*

*Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas; and Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California

Address correspondence and reprint requests to Maria Paola Mascia, PhD, Institute for Cellular and Molecular Biology, University of Texas, 2500 Speedway MBB 1.124, Austin, TX 78712-1095. Address e-mail to mariapaola{at}mail.utexas.edu

Although similar in shape and size, and although differing only by substitution of a sulfur atom for an oxygen atom, propanethiol and butanethiol differ markedly from propanol and butanol in their in vivo potency and physical properties. Recent theories of narcosis suggest that anesthetics may act by enhancing the effect of inhibitory agonists, such as glycine, on their receptors. We tested whether propanol, butanol, propanethiol, and butanethiol enhance the effect of glycine on 1 glycine receptors expressed in Xenopus laevis oocytes in a manner that reflects the in vivo differences found for potencies. As anticipated, we found an immediate parallel between in vivo (rat minimum alveolar concentration of anesthetic required to eliminate movement in response to a noxious stimulus in 50% of subjects) and in vitro (recombinant receptor) effects. All four compounds enhanced the effect of glycine on wild type receptors, and the extent of enhancement for a given minimum alveolar concentration-multiple was approximately the same for all compounds. We also found that propanethiol, butanethiol, propanol, and butanol did not affect, or minimally affected, the action of glycine in anesthetic resistant mutants in which the amino acid serine at position 267 was replaced by glutamine [1(S267Q)].

Implications: The in vivo potencies of propanethiol, butanethiol, propanol, and butanol correlate with their capacities to enhance the effect of glycine on 1 glycine receptors expressed in Xenopus laevis oocytes. These results support the notion that a protein mediates anesthetic action.

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